1.Effects of long-term endurance exercise on kl/FGF23 axis and calcium-phosphorus metabolism in naturally aging mice
Tuanhui PENG ; Hongming SONG ; Ling YANG ; Xiaoge DING ; Pengjun MENG
Chinese Journal of Tissue Engineering Research 2026;30(5):1089-1095
BACKGROUND:Studies have shown that disorders of mineral metabolism may be responsible for premature aging and that the kl/FGF23 axis plays an important role in mineral metabolism.OBJECTIVE:To explore the effect of long-term endurance exercise on the kl/FGF23 axis in naturally aging mice,and to observe the impact of long-term endurance exercise on calcium and phosphorus metabolism,so as to provide a reference for the influence of long-term endurance exercise on natural aging.METHODS:Twenty-two 5-week-old SPF male balb/c mice were randomly divided into three groups:young and quiet control group,natural aging quiet group and natural aging exercise group.Mice in the young and quiet control group were then killed immediately.Mice in the natural aging quiet group were raised normally until 60 weeks of age.Mice in the natural aging exercise group were subjected to adaptive exercise for 1 week,followed by the maximum running speed test.The official exercise speed was set at 70%of the maximum running speed,and exercise was performed on Mondays,Wednesdays,and Fridays for 50 minutes each.Maximum running speed was retested at 8-week intervals to adjust the official exercise speed until the age of 60 weeks.(3)Enzyme-linked immunoassay was used to measure the levels of femoral fibroblast growth factor 23,renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2D3.RESULTS AND CONCLUSION:(1)Compared with the young and quiet control group,serum calcium and phosphorus levels in natural aging quiet group had no significant changes(P>0.05),but bone calcium and phosphorus levels were significantly reduced(P<0.01).Compared with the natural aging quiet group,the serum phosphorus level was significantly reduced(P<0.05),the serum calcium level did not change(P>0.05),and bone calcium and phosphorus levels were significantly increased in the natural aging exercise group(P<0.05).(2)Compared with the young and quiet control group,the level of fibroblast growth factor 23 in the femur of the natural aging quiet group was significantly increased(P<0.05).Compared with the natural aging quiet group,the level of fibroblast growth factor 23 in the femur of the natural aging exercise group was reduced,but it was not statistically significant(P>0.05).(3)Compared with the young and quiet control group,the renal Klotho protein expression,the renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2 D3 levels in the natural aging quiet group were significantly decreased(P<0.05,P<0.01).Compared with the natural aging quiet group,the levels of the above-mentioned indicators were significantly increased in the natural aging exercise group(P<0.05,P<0.01).To conclude,long-term endurance exercise can regulate Klotho protein and fibroblast growth factor 23 through the kl/FGF23 axis,thereby affecting the expression of 1α-hydroxylase and the level of 1,25(OH)2D3,and further regulating the body's calcium and phosphorus metabolism,especially phosphate metabolism.This indicates that long-term endurance exercise can delay the natural aging of the body through the kl/FGF23 axis.
2.Effects of SPBC1604.04 Gene Deletion on Mitotic Cell Dynamics in Schizosaccharomyces pombe
Jia-Ni XU ; Jia-Yi HE ; Lang-Lin ZHENG ; Shu-Rong HE ; Shuai MA ; Xiang DING ; Yi-Ling HOU
Progress in Biochemistry and Biophysics 2026;53(5):1471-1484
ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.
3.Effects of SPBC1604.04 Gene Deletion on Mitotic Cell Dynamics in Schizosaccharomyces pombe
Jia-Ni XU ; Jia-Yi HE ; Lang-Lin ZHENG ; Shu-Rong HE ; Shuai MA ; Xiang DING ; Yi-Ling HOU
Progress in Biochemistry and Biophysics 2026;53(5):1471-1484
ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.
4.Effects of long-term endurance exercise on kl/FGF23 axis and calcium-phosphorus metabolism in naturally aging mice
Tuanhui PENG ; Hongming SONG ; Ling YANG ; Xiaoge DING ; Pengjun MENG
Chinese Journal of Tissue Engineering Research 2026;30(5):1089-1095
BACKGROUND:Studies have shown that disorders of mineral metabolism may be responsible for premature aging and that the kl/FGF23 axis plays an important role in mineral metabolism.OBJECTIVE:To explore the effect of long-term endurance exercise on the kl/FGF23 axis in naturally aging mice,and to observe the impact of long-term endurance exercise on calcium and phosphorus metabolism,so as to provide a reference for the influence of long-term endurance exercise on natural aging.METHODS:Twenty-two 5-week-old SPF male balb/c mice were randomly divided into three groups:young and quiet control group,natural aging quiet group and natural aging exercise group.Mice in the young and quiet control group were then killed immediately.Mice in the natural aging quiet group were raised normally until 60 weeks of age.Mice in the natural aging exercise group were subjected to adaptive exercise for 1 week,followed by the maximum running speed test.The official exercise speed was set at 70%of the maximum running speed,and exercise was performed on Mondays,Wednesdays,and Fridays for 50 minutes each.Maximum running speed was retested at 8-week intervals to adjust the official exercise speed until the age of 60 weeks.(3)Enzyme-linked immunoassay was used to measure the levels of femoral fibroblast growth factor 23,renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2D3.RESULTS AND CONCLUSION:(1)Compared with the young and quiet control group,serum calcium and phosphorus levels in natural aging quiet group had no significant changes(P>0.05),but bone calcium and phosphorus levels were significantly reduced(P<0.01).Compared with the natural aging quiet group,the serum phosphorus level was significantly reduced(P<0.05),the serum calcium level did not change(P>0.05),and bone calcium and phosphorus levels were significantly increased in the natural aging exercise group(P<0.05).(2)Compared with the young and quiet control group,the level of fibroblast growth factor 23 in the femur of the natural aging quiet group was significantly increased(P<0.05).Compared with the natural aging quiet group,the level of fibroblast growth factor 23 in the femur of the natural aging exercise group was reduced,but it was not statistically significant(P>0.05).(3)Compared with the young and quiet control group,the renal Klotho protein expression,the renal fibroblast growth factor receptor 1,1α-hydroxylase,and serum 1,25(OH)2 D3 levels in the natural aging quiet group were significantly decreased(P<0.05,P<0.01).Compared with the natural aging quiet group,the levels of the above-mentioned indicators were significantly increased in the natural aging exercise group(P<0.05,P<0.01).To conclude,long-term endurance exercise can regulate Klotho protein and fibroblast growth factor 23 through the kl/FGF23 axis,thereby affecting the expression of 1α-hydroxylase and the level of 1,25(OH)2D3,and further regulating the body's calcium and phosphorus metabolism,especially phosphate metabolism.This indicates that long-term endurance exercise can delay the natural aging of the body through the kl/FGF23 axis.
5.Related factors and pathway analysis of e-cigarette use behavior among primary and secondary school students in Pudong New Area,Shanghai
Chinese Journal of School Health 2026;47(6):795-798
Objective:
To examine the prevalence of e-cigarette use and associated factors among primary and secondary school students in Pudong New Area, Shanghai, and to explore the pathways linking harm perception of e-cigarettes, interpersonal social influence, and attitudes toward e-cigarette use with experimentation behavior, in order to provide scientific basis for further optimizing the prevention and control strategies of e-cigarette among adolescents.
Methods:
From September to October 2025, a multi stage cluster random sampling method was used to select 5 144 primary and secondary school students aged 8-19 years from 47 primary and secondary schools in Pudong New Area, Shanghai, to conduct an anonymous questionnaire survey. The questionnaire collected information on e-cigarette use, harm perception of e-cigarette, interpersonal social influence, and attitudes toward e-cigarette use. The Chi-square test was applied to analyze the differences in cigarette and e-cigarette use behavior among primary and secondary school students with different demographic characteristics. Structural equation modeling (SEM) was constructed using Mplus 8.3 software, and the bootstrap method was utilized to test the mediating effects.
Results:
The reported rates of cigarette experimentation, e-cigarette experimentation, and current e-cigarette use among primary and secondary school students were 1.85%, 2.10%, and 0.70%, respectively. Higher reporting rates of e-cigarette experimentation were observed among boys (2.82%), secondary school students aged 16-19 (3.39%), senior high school students (3.05%), and those with weekly pocket money >100 yuan ( 6.11% ) ( χ 2=11.67, 8.61, 8.00, 54.18, all P <0.05). Structural pathway analysis results demonstrated that e-cigarette harm perception positively predicted interpersonal social influence ( β =0.61) and e-cigarette use attitude ( β = 0.53 ), and interpersonal social influence ( β =0.65) and e-cigarette use attitude ( β =0.25) further promoted e-cigarette experimentation behavior among primary and secondary school students (all P <0.01), with interpersonal social influence playing a major mediating role (indirect effect=0.40).
Conclusions
E-cigarette experimentation behavior among primary and secondary school students in Pudong New Area is jointly influenced by multiple psychosocial factors. Intervention strategies should strengthen interpersonal social factors such as family and peers on the basis of health education, thereby constructing a comprehensive prevention and control strategy for e-cigarette use among primary and secondary school students.
6.Effects of volatile oil from Acorus tatarinowii on CX3CL1/CX3CR1 signal axis and neuroinflammation in a rat model of tic disorders
Yan-qin DING ; Peng FENG ; Ming-lu WANG ; Yu-tong WANG ; Ke-xin SUN ; Xing WEI ; Yong-yan TIAN ; Xing-ping TANG ; Ping LI ; Ruo-lan LU ; Ling LI
Chinese Traditional Patent Medicine 2025;47(6):1825-1833
AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P<0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P<0.05,P<0.01);decreased levels of TNF-α and IL-1β(P<0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P<0.01);increased protein expressions of PSD95 and SYN(P<0.05,P<0.01);and decreased CD86/Iba1(P<0.01)and increased CD206/Iba1(P<0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.
7.Analysis of the Medication Pattern of Traditional Chinese Medicine Prescriptions for 159 Cases of Pediatric Mesenteric Lymphadenitis
Yu-ting YANG ; Qing-ling DING ; Ran ZHANG
Progress in Modern Biomedicine 2025;25(12):1976-1982
Objective:To analyze the medication pattern of traditional chinese medicine for pediatric mesenteric lymphadenitis,and to provide medication reference for clinical treatment of this disease.Methods:A total of 159 traditional chinese medicine prescriptions who were diagnosed with pediatric mesenteric lymphadenitis in the outpatient department of the Traditional Chinese Medicine Department of Chongqing Medical University Affiliated Children's Hospital from January 2020 to March 2024 were collected.A medication database was created by Excel software,and the high-frequency application of traditional chinese medicine,four qi of traditional chinese medicine,five flavors,meridian tropism,correlation analysis,and cluster analysis were analyzed by ancient and modern medical case cloud platform and SPSS software.Results:The top 10 drugs in terms of frequency were licorice,hawthorn,tangerine peel,corydalis yanhusuo,malt,white peony,magnolia officinalis,poria cocos,atractylodes macrocephala,and forsythia suspensa.The top three medicinal properties were warm,calm,and cold.The top three medicinal flavors were sweet,spicy,and bitter.The top three drugs classified by meridian were spleen,lung,and stomach.Association rule analysis identified four groups of core drugs.Cluster analysis divides high-frequency traditional Chinese medicine into four effective prescription groups.Conclusion:Traditional chinese medicine treatment for pediatric mesenteric lymphadenitis,association rule analysis has identified core drug combinations,including licorice,hawthorn,tangerine peel,etc;Cluster analysis divides high-frequency traditional chinese medicine into four groups of prescriptions,with the treatment methods of regulating qi and strengthening spleen,strengthening spleen and eliminating dampness,clearing heat and detoxifying,and promoting qi and blood circulation,providing reference for the rational application of traditional chinese medicine in the treatment of pediatric mesenteric lymphadenitis in clinical practice.
8.Diagnostic value of the combination of serum neutrophil CD64,CRP and LDH in children with refractory Mycoplasma pneumoniae pneumonia
E WANG ; Pei ZHANG ; Ying HUO ; Jialing JI ; Ling DING ; Aiqing ZHANG
Tianjin Medical Journal 2025;53(12):1246-1250
Objective To investigate the value of the combined detection of neutrophil CD64(nCD64),C-reactive protein(CRP)and lactate dehydrogenase(LDH)in the diagnosis of refractory Mycoplasma pneumoniae pneumonia(RMPP)in children.Methods A total of 147 children with Mycoplasma pneumoniae infection were enrolled and divided into the RMPP group(n=70)and the general Mycoplasma pneumoniae pneumonia group(GMPP,n=77)based on disease severity and treatment response.The age,gender,white blood cell count(WBC)within 24 hours of admission,serum procalcitonin(PCT),C-reactive protein(CRP)and lactate dehydrogenase(LDH)levels were collected in the study participants.The expression level of nCD64 in peripheral blood was measured using flow cytometry.Multivariate Logistic regression analysis was conducted to identify the independent risk factors associated with RMPP in children.Additionally,a receiver operating characteristic(ROC)curve was constructed to assess the diagnostic performance of the combined detection of nCD64,CRP and LDH for RMPP in children.Results The RMPP group had a longer hospital stay than the GMPP group(P<0.05).Levels of nCD64,CRP and LDH were significantly higher in the RMPP group compared to those of the GMPP group(P<0.05),and there were no significant differences in WBC and PCT levels between the two groups.Multivariate Logistic regression analysis showed that elevated nCD64,CRP and LDH were risk factors for RMPP in children(P<0.05).ROC curve analysis revealed that the areas under the curve(AUC)for nCD64,CRP and LDH in diagnosing RMPP were 0.817,0.863 and 0.805,respectively.The combined detection of three indicators for AUC was 0.948.Conclusion The levels of nCD64,CRP and LDH in blood of children with RMPP are higher than those of children with GMPP.The combined detection of the three indicators has a high diagnostic value for RMPP in children with Mycoplasma pneumoniae pneumonia.
9.Trend analysis of breast cancer burden in China and the United States from 1990 to 2021
Mao YUN ; Zhang WANHUI ; Deng QIANLING ; Ding ZHIXUN ; Fu LING ; Hu BEIER ; Cao WEN
Chinese Journal of Clinical Oncology 2025;52(17):884-891
Objective:To investigate the disparities in breast cancer burden and changing epidemiological trends between China and the United States(US)from 1990 to 2021 and identify the key driving factors.Methods:The Global Burden of Disease database(1990-2021)was utilized to analyze breast cancer incidence,mortality,and disability adjusted life years(DALYs)in China and the US;we also assessed the as-sociations with risk factors(e.g.,obesity and smoking)through regression models and spatiotemporal analysis.Results:China's breast can-cer age-standardized incidence rate(ASIR)surged from 9.08/100,000 in 1990 to 19.36/100,000 in 2021,whereas the US ASIR declined from 44.37/100,000 to 37.49/100,000.Regarding the age-standardized mortality rate(ASMR),China saw a marginal reduction from 4.70/100,000 to 4.40/100,000,whereas the US experienced a significant decline from 13.03/100,000 to 9.28/100,000,narrowing the mortality gap from 2.8-fold to 2.1-fold.Key risk factors contributing to mortality and DALYs included smoking,exposure to secondhand smoke,low physical activity,high red meat and alcohol intake,elevated fasting blood glucose levels,and high body mass index.The rising cancer incidence in China is associated with the westernization of lifestyles and changes in fertility patterns,whereas the United States has achieved a dual de-cline in both incidence and mortality rates through widespread screening and control of hormone replacement therapy.Conclusions:Both the incidence and mortality rates of breast cancer in China rank among the highest globally,with incidence rates still increasing,indicating severe issues in prevention and control.In contrast,although the incidence rate in the US is higher than that in China,it shows a declining trend.To alleviate the growing burden of breast cancer,China must further enhance the intensity and coverage of breast cancer screening.
10.The Histone Methyltransferase EZH2 is Downregulated in the Terminal Differentiation of Cardiomyocytes
Wan-Yi ZHANG ; Wan-Lei ZHANG ; Yuan-Yuan LIU ; Ling-Er DING ; Qi-Kai TANG ; Zhen-Hang LI ; Hao-Ying YANG ; Tao LI
Chinese Journal of Biochemistry and Molecular Biology 2025;41(3):415-425
Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P<0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P<0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P<0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P<0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P<0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P<0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.


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