1.Correlation of bone mineral density, serum TGF- β1, and RBP4 levels with osteoporosis in gestational diabetes mellitus
Yu LIU ; Qing LIU ; Fang WANG ; Na DONG ; Yanying XU
Chinese Journal of Endocrine Surgery 2025;19(2):248-251
Objective:To analyze the correlation of bone mineral density (BMD) , serum transforming growth factor β1 (TGF- β1) , and retinol-binding protein 4 (RBP4) with osteoporosis in gestational diabetes mellitus (GDM) . Methods:A total of 180 GDM patients admitted to Department of Gynecology, Second Hospital of Tianjin Medical University from Jan. 2022 to Jan. 2024 were included as the observation group, and 30 healthy pregnant women undergoing examination at the same time were included into the control group. BMD [stiffness index (SI) , broadband ultrasound attenuation (BUA) , speed of sound (SOS) ], serum TGF-β1, and RBP4 levels were compared between the two groups; GDM women with complicated with osteoporosis were included in the osteoporosis subgroup, and pregnant women without osteoporosis were included in the non-osteoporosis subgroup. BMD, serum TGF- β1 and RBP4 levels were compared between the two groups, and the relationship among bone mineral density and serum TGF- β1, RBP4 was analyzed by Pearson correlation. Receiver operating characteristic curve (ROC) curve was drawn to evaluate the diagnostic value of serum TGF- β1 and RBP4 levels in GDM complicated with osteoporosis. Results:The observation group had significantly higher levels of serum TGF- β1 and RBP4 than the control group, while lower BUA, SOS and SI ( t=99.04, 28.48, 4.10, 3.54, 6.29, P < 0.05) ; Among 180 pregnant women with GDM, 38 cases had osteoporosis and 142 cases did not have osteoporosis. The osteoporosis subgroup had significantly higher serum TGF- β1 and RBP4 levels than the other subgroup, while BMD indexes such as BUA, SOS and SI were significantly lower ( t=3.35, 3.48, 3.77, 2.85, 3.41, P < 0.05) ; Pearson correlation analysis showed that BMD indexes, such as BUA, SOS and SI, were significantly correlated with serum TGF- β1 and RBP4 in pregnant women with GDM ( r=-0.61, 0.58, -0.60, -0.58, -0.60, -0.63, P<0.05) ; The area under the curve (AUC) of TGF- β1, RBP4 and combined detection of GDM women with osteoporosis was 0.572, 0.653 and 0.659, respectively. Conclusions:In GDM women complicated with osteoporosis, the levels of serum TGF- β1 and RBP4 increase significantly, and BMD decreases significantly. Serum TGF- β1 and RBP4 in GDM women are closely related to BMD index, which can provide early diagnosis basis for GDM complicated with osteoporosis.
2.Orbital eosinophilic angiocentric fibrosis: a case report with literature review
Chengye LIANG ; Yuetong XU ; Tianqi WANG ; Yan SUN ; Penggang QIAO ; Yanying LIU
Chinese Journal of Rheumatology 2025;29(3):219-224
Objective:To analyze the clinical characteristics and treatment of eosinophilic angiocentric fibrosis (EAF) involving the orbit.Methods:We described a case and review the literature of EAF involving the orbit.Results:The literature review has shown 34 similar cases. Nineteen patients combined with other site involvement (17 cases had nasal involvement), whereas 15 had primary orbital involvement. Ocular swelling (18 cases) and epiphora (4 cases) were the most common initial presenting symptoms. The typical histopathologic findings include a perivascular, eosinophil-rich infiltrate and a "onion-skin" type of fibrosis concentrated around small vessels and all cases in this group conformed the above typical characteristics. In this series, 20 patients provided immunohistochemical results for IgG4, among them, 16 cases were positive while 4 cases were negative. No manifestations of obliterative phlebitis and storiform fibrosis were observed. The age, gender, and lesion locations (single or multiple) of the IgG4 staining positive group and the negative group were analyzed. There was no statistically significant difference in the age of onset, gender ratio and lesion the two groups ( P>0.05). Conclusion:For patients presented with ocular swelling, epiphora, with or without nasal lesions, EAF should be considered. The diagnosis of EAF is based largely on histopathologic findings. Although some cases were positive for IgG4 by immunohistochemistry, storiform fibrosis and obliterative phlebitis is not seen in our series, which aid in distinguishing EAF from IgG4-related disease.
3.Correlation of bone mineral density, serum TGF- β1, and RBP4 levels with osteoporosis in gestational diabetes mellitus
Yu LIU ; Qing LIU ; Fang WANG ; Na DONG ; Yanying XU
Chinese Journal of Endocrine Surgery 2025;19(2):248-251
Objective:To analyze the correlation of bone mineral density (BMD) , serum transforming growth factor β1 (TGF- β1) , and retinol-binding protein 4 (RBP4) with osteoporosis in gestational diabetes mellitus (GDM) . Methods:A total of 180 GDM patients admitted to Department of Gynecology, Second Hospital of Tianjin Medical University from Jan. 2022 to Jan. 2024 were included as the observation group, and 30 healthy pregnant women undergoing examination at the same time were included into the control group. BMD [stiffness index (SI) , broadband ultrasound attenuation (BUA) , speed of sound (SOS) ], serum TGF-β1, and RBP4 levels were compared between the two groups; GDM women with complicated with osteoporosis were included in the osteoporosis subgroup, and pregnant women without osteoporosis were included in the non-osteoporosis subgroup. BMD, serum TGF- β1 and RBP4 levels were compared between the two groups, and the relationship among bone mineral density and serum TGF- β1, RBP4 was analyzed by Pearson correlation. Receiver operating characteristic curve (ROC) curve was drawn to evaluate the diagnostic value of serum TGF- β1 and RBP4 levels in GDM complicated with osteoporosis. Results:The observation group had significantly higher levels of serum TGF- β1 and RBP4 than the control group, while lower BUA, SOS and SI ( t=99.04, 28.48, 4.10, 3.54, 6.29, P < 0.05) ; Among 180 pregnant women with GDM, 38 cases had osteoporosis and 142 cases did not have osteoporosis. The osteoporosis subgroup had significantly higher serum TGF- β1 and RBP4 levels than the other subgroup, while BMD indexes such as BUA, SOS and SI were significantly lower ( t=3.35, 3.48, 3.77, 2.85, 3.41, P < 0.05) ; Pearson correlation analysis showed that BMD indexes, such as BUA, SOS and SI, were significantly correlated with serum TGF- β1 and RBP4 in pregnant women with GDM ( r=-0.61, 0.58, -0.60, -0.58, -0.60, -0.63, P<0.05) ; The area under the curve (AUC) of TGF- β1, RBP4 and combined detection of GDM women with osteoporosis was 0.572, 0.653 and 0.659, respectively. Conclusions:In GDM women complicated with osteoporosis, the levels of serum TGF- β1 and RBP4 increase significantly, and BMD decreases significantly. Serum TGF- β1 and RBP4 in GDM women are closely related to BMD index, which can provide early diagnosis basis for GDM complicated with osteoporosis.
4.Expression and clinical significance of non-coding RNA GATA binding protein 6 antisense RNA1 and GATA binding protein 6 messenger RNA in ovarian cancer
Fengzhen CHEN ; Yanying XU ; Na DONG ; Lei TIAN
Chinese Journal of Postgraduates of Medicine 2025;48(11):987-992
Objective:To investigate the expression and clinical significance of non coding RNA GATA binding protein 6 antisense RNA1 (lncRNA GATA6-AS1) and GATA binding protein 6 messenger RNA (GATA6 mRNA) in ovarian cancer.Methods:A prospective study was conducted on 98 patients with ovarian cancer treated at the Second Hospital of Tianjin Medical University, from January 2022 to January 2025, and 98 patients with benign ovarian lesions during the same period were selected as the control group. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the serum and tissue expression levels of lncRNA GATA6-AS1 and GATA6 mRNA in patients with ovarian cancer and benign ovarian lesions. Pearson analysis was performed to assess the correlation between serum lncRNA GATA6-AS1 and GATA6 mRNA levels in patients with ovarian cancer. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of serum lncRNA GATA6-AS1 and GATA6 mRNA levels in patients with ovarian cancer.Results:Compared with the control group, the serum levels of lncRNA GATA6-AS1 and GATA6 mRNA in the study group were decreased: 0.76 ± 0.18 vs. 1.00 ± 0.22, 0.75 ± 0.19 vs. 1.01 ± 0.21, with statistically significant differences ( P<0.05). Pearson analysis revealed a positive correlation between serum lncRNA GATA6-AS1 and GATA6 mRNA levels in the study group ( r = 0.61, P<0.05). Compared with benign ovarian lesion tissues, the expression levels of lncRNA GATA6-AS1 and GATA6 mRNA in ovarian cancer tissues were reduced: 0.65 ± 0.15 vs. 1.01 ± 0.20, 0.59 ± 0.12 vs. 1.01 ± 0.24, with statistically significant differences ( P<0.05). In serous ovarian cancer tissues, the expression levels of lncRNA GATA6-AS1 and GATA6 mRNA were lower than those in mucinous ovarian cancer tissues: 0.61 ± 0.10 vs. 0.77 ± 0.16, 0.54 ± 0.11 vs. 0.74 ± 0.14, with statistically significant differences ( P<0.05). The expression of lncRNA GATA6-AS1 and GATA6 mRNA in ovarian cancer tissues was associated with tumor size, International Federation of Gynecology and Obstetrics stage, differentiation degree, lymph node metastasis, peritoneal metastasis, and ascites ( P<0.05). The ROC curve indicated that the combined diagnosis of serum lncRNA GATA6-AS1 and GATA6 mRNA for ovarian cancer had an area under the curve (AUC) of 0.905, which was significantly higher than that of lncRNA GATA6-AS1 alone ( Z = 2.45, P = 0.014) and GATA6 mRNA alone ( Z = 2.16, P = 0.031). Conclusions:The lncRNA GATA6-AS1 and GATA6 mRNA in serum and tissue of ovarian cancer patients decrease, showing a positive correlation. The joint of the two has high diagnostic value for ovarian cancer.
5.Expression and clinical significance of non-coding RNA GATA binding protein 6 antisense RNA1 and GATA binding protein 6 messenger RNA in ovarian cancer
Fengzhen CHEN ; Yanying XU ; Na DONG ; Lei TIAN
Chinese Journal of Postgraduates of Medicine 2025;48(11):987-992
Objective:To investigate the expression and clinical significance of non coding RNA GATA binding protein 6 antisense RNA1 (lncRNA GATA6-AS1) and GATA binding protein 6 messenger RNA (GATA6 mRNA) in ovarian cancer.Methods:A prospective study was conducted on 98 patients with ovarian cancer treated at the Second Hospital of Tianjin Medical University, from January 2022 to January 2025, and 98 patients with benign ovarian lesions during the same period were selected as the control group. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the serum and tissue expression levels of lncRNA GATA6-AS1 and GATA6 mRNA in patients with ovarian cancer and benign ovarian lesions. Pearson analysis was performed to assess the correlation between serum lncRNA GATA6-AS1 and GATA6 mRNA levels in patients with ovarian cancer. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of serum lncRNA GATA6-AS1 and GATA6 mRNA levels in patients with ovarian cancer.Results:Compared with the control group, the serum levels of lncRNA GATA6-AS1 and GATA6 mRNA in the study group were decreased: 0.76 ± 0.18 vs. 1.00 ± 0.22, 0.75 ± 0.19 vs. 1.01 ± 0.21, with statistically significant differences ( P<0.05). Pearson analysis revealed a positive correlation between serum lncRNA GATA6-AS1 and GATA6 mRNA levels in the study group ( r = 0.61, P<0.05). Compared with benign ovarian lesion tissues, the expression levels of lncRNA GATA6-AS1 and GATA6 mRNA in ovarian cancer tissues were reduced: 0.65 ± 0.15 vs. 1.01 ± 0.20, 0.59 ± 0.12 vs. 1.01 ± 0.24, with statistically significant differences ( P<0.05). In serous ovarian cancer tissues, the expression levels of lncRNA GATA6-AS1 and GATA6 mRNA were lower than those in mucinous ovarian cancer tissues: 0.61 ± 0.10 vs. 0.77 ± 0.16, 0.54 ± 0.11 vs. 0.74 ± 0.14, with statistically significant differences ( P<0.05). The expression of lncRNA GATA6-AS1 and GATA6 mRNA in ovarian cancer tissues was associated with tumor size, International Federation of Gynecology and Obstetrics stage, differentiation degree, lymph node metastasis, peritoneal metastasis, and ascites ( P<0.05). The ROC curve indicated that the combined diagnosis of serum lncRNA GATA6-AS1 and GATA6 mRNA for ovarian cancer had an area under the curve (AUC) of 0.905, which was significantly higher than that of lncRNA GATA6-AS1 alone ( Z = 2.45, P = 0.014) and GATA6 mRNA alone ( Z = 2.16, P = 0.031). Conclusions:The lncRNA GATA6-AS1 and GATA6 mRNA in serum and tissue of ovarian cancer patients decrease, showing a positive correlation. The joint of the two has high diagnostic value for ovarian cancer.
6.Orbital eosinophilic angiocentric fibrosis: a case report with literature review
Chengye LIANG ; Yuetong XU ; Tianqi WANG ; Yan SUN ; Penggang QIAO ; Yanying LIU
Chinese Journal of Rheumatology 2025;29(3):219-224
Objective:To analyze the clinical characteristics and treatment of eosinophilic angiocentric fibrosis (EAF) involving the orbit.Methods:We described a case and review the literature of EAF involving the orbit.Results:The literature review has shown 34 similar cases. Nineteen patients combined with other site involvement (17 cases had nasal involvement), whereas 15 had primary orbital involvement. Ocular swelling (18 cases) and epiphora (4 cases) were the most common initial presenting symptoms. The typical histopathologic findings include a perivascular, eosinophil-rich infiltrate and a "onion-skin" type of fibrosis concentrated around small vessels and all cases in this group conformed the above typical characteristics. In this series, 20 patients provided immunohistochemical results for IgG4, among them, 16 cases were positive while 4 cases were negative. No manifestations of obliterative phlebitis and storiform fibrosis were observed. The age, gender, and lesion locations (single or multiple) of the IgG4 staining positive group and the negative group were analyzed. There was no statistically significant difference in the age of onset, gender ratio and lesion the two groups ( P>0.05). Conclusion:For patients presented with ocular swelling, epiphora, with or without nasal lesions, EAF should be considered. The diagnosis of EAF is based largely on histopathologic findings. Although some cases were positive for IgG4 by immunohistochemistry, storiform fibrosis and obliterative phlebitis is not seen in our series, which aid in distinguishing EAF from IgG4-related disease.
7.Repairing Effects of Ginsenoside Rg1 on Traumatic Brain Injury in Mice
Wenwen GUO ; Ya ZHAO ; Yinghua WANG ; Ke LIU ; Xu GE ; Yanying ZHANG ; Yongfeng WANG ; Changhong SHI
Laboratory Animal and Comparative Medicine 2023;43(3):243-252
Objective To explore the effects of ginsenoside Rg1 on blood-brain barrier, neuroinflammation and behavioral function of traumatic brain injury (TBI) mouse model.MethodsThe experiment was divided into two parts. In the first part, 27 SPF male BALB/c mice were randomly divided into blank group, sham operation group and TBI model group, with 9 mice in each group. TBI model group was made by controlled cortical impact (CCI) after craniotomy, while sham operation group was only performed craniotomy without any treatment, and the blank group was not treated at all. The effect of modeling was evaluated after operation. In the second part, 50 male BALB/c mice were randomly divided into sham operation group, three different drug dosage groups and solvent (DMSO) control group, with 8 mice in each group. The drug treatment groups were injected with ginsenoside Rg1 at the doses of 10, 20 and 40 mg/kg respectively 6 hours after TBI model had been successfully established, while the DMSO control group was given the same amount of 1% DMSO for one week, twice a day. Modified neurological severity scores (mNSS) were performed on the 1st, 3rd, 7th and 14th day after modeling, and the blood-brain barrier leakage was detected by Western blotting on the 3rd day after modeling. On the 14th and 16th day, the elevated cross maze test and water maze test were used to detect the neurobehavioral function. On the 28th day after anesthesia and perfusion, the brains were taken out, and the neuroinflammation such as activation of microglia and astrocytes was observed by immunofluorescence staining.ResultsThe expression level of MMP-9, a marker of blood-brain barrier, decreased in ginsenoside Rg1 treatment group (P<0.01). The number of microglia (Iba-1 positive) and astrocyte (GFAP positive) cells decreased significantly (P<0.05), which indicated that neuroinflammation was inhibited, and the best effect was achieved at the dosage of 20 mg/kg (P<0.01). The mNSS of mice in ginsenoside Rg1 treatment group were significantly lower than those in DMSO control group (P < 0.01), and the proportion of times they entered the open arm was significantly higher than that in DMSO control group (P < 0.05). The time ratio in the quadrant where the water maze experimental platform was located and the times of crossing the platform were significantly higher than those in control group (P < 0.05), and the dosage of 20 mg/kg had the best effect.ConclusionThe TBI mouse model was successfully constructed and applied to the study of ginsenoside Rg1 repair of mouse traumatic brain injury. Ginsenoside Rg1 can significantly improve blood-brain barrier, alleviate neuroinflammation and improve neurobehavioral function in TBI model mice, and the effect is the most significant at the dose of 20 mg/kg.
8.Value of fibrosis-4 combined with prognostic nutritional index in predicting recurrence and survival time after radiofrequency ablation for early-stage hepatocellular carcinoma
Xu ZHANG ; Fushuang HA ; Fenghui LI ; Yanying GAO ; Jing LIANG
Journal of Clinical Hepatology 2023;39(11):2614-2622
ObjectiveTo investigate the value of preoperative fibrosis 4 score (FIB-4) combined with prognostic nutritional index (PNI) in predicting recurrence after radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC). MethodsA retrospective analysis was performed for the clinical data of 365 patients with the initial diagnosis of early-stage HCC who underwent RFA at Tianjin Third Central Hospital from January 2013 to December 2017, and a statistical analysis was performed for recurrence and survival. The receiver operating characteristic (ROC) curve was plotted for FIB-4 and PNI with postoperative tumor recurrence as the positive event, and their optimal cut-off values were selected. FIB-4 and PNI were graded and combined as FIB-4-PNI score, based on which the patients were divided into 0-point group with 207 patients, 1-point group with 93 patients, and 2-point group with 65 patients. The chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier survival analysis and the log-rank test were used to compare the recurrence-free survival (RFS) and overall survival (OS) between groups, and the Cox regression model was used to investigate the influencing factors for RFS and OS. ResultsThe 1-, 3-, and 5-year RFS rates of all patients were 79.2%, 49.8%, and 34.3%, respectively, with a median RFS of 35 months, while the 1-, 3-, and 5-year OS rates of all patients were 98.9%, 86.9%, and 77.3%, respectively. There were significant differences in cumulative RFS and OS rates between the patients with different levels of FIB-4, PNI, and FIB-4-PNI (RFS rate: χ2=17.890, 29.826, and 32.397, all P<0.001; OS rate: χ2=16.896, 21.070, and 26.121, all P<0.001). The multivariate Cox regression analysis showed that history of diabetes (hazard ratio [HR]=1.418, 95% confidence interval [CI]: 1.046 — 1.922, P=0.024), two tumors (HR=1.516, 95%CI: 1.094 — 2.101, P=0.012), three tumors (HR=2.146, 95%CI: 1.278 — 3.604, P=0.004), FIB-4-PNI 1 point (HR=1.875, 95%CI: 1.385 — 2.539, P<0.001), and FIB-4-PNI 2 points (HR=2.35, 95%CI: 1.706 — 3.236, P<0.001) were independent risk factors for RFS, while two tumors (HR=1.732, 95%CI: 1.005 — 2.983, P=0.048), three tumors (HR=3.511, 95%CI: 1.658 — 7.433, P=0.001), FIB-4-PNI 1 point (HR=2.094, 95%CI: 1.230 — 3.565, P=0.006), and FIB-4-PNI 2 points (HR=3.908, 95%CI: 2.306 — 6.624, P<0.001) were independent risk factors for OS. ConclusionFIB-4-PNI score can be used as an independent predictive factor for recurrence and overall survival time after RFA for early-stage HCC, and it can be combined with tumor features to predict postoperative recurrence and survival.
9.Effect of lysophosphatidic acid on hepatoma cells and related mechanism
Yanying ZHAO ; Zhenqi HAN ; Yanping ZOU ; Yunpeng LI ; Tao XU ; Liyan LIU ; Haitao CHENG
Journal of Clinical Hepatology 2023;39(11):2623-2628
ObjectiveTo investigate the expression of lysophosphatidic acid (LPA) in patients with liver cancer, as well as its influence on malignant biological behavior of liver cancer and related regulatory mechanism. MethodsFrom January 2016 to December 2022, 26 patients with liver cancer, 28 patients with liver cirrhosis, and 28 individuals undergoing physical examination were enrolled. ELISIA was used to measure the content of LPA in plasma and peritoneal effusion of the patients with liver cancer or liver cirrhosis accompanied by peritoneal effusion, and the content of LPA was measured in plasma of the normal population at the same time, so as to clarify the difference in the expression of LPA in different populations, such as the patients with liver cancer and those with liver cirrhosis. MTT cell proliferation assay and cell migration assay were used to observe the influence of LPA and its inhibitor pertussis toxin (PTX) on the proliferation, migration, and invasion of SMMC7721 cells. In order to investigate the effect of LPA on the expression of RhoA and its upstream and downstream molecules FAK and P53 after binding to its receptor, qPCR and Western blot were used to observe the effect of LPA on the mRNA and protein expression levels of P53, FAK, and RhoA in SMMC7721 cells. A one-way analysis of variance was used for comparison of the means of continuous data between multiple groups, and the SNK-q test was used for comparison between two groups. ResultsCompared with the patients with liver cirrhosis, the patients with liver cancer had a significantly higher concentration of LPA in plasma (4.99±0.55 μmol/L vs 2.63±0.43 μmol/L, P<0.05) and peritoneal effusion (5.19±0.63 μmol/L vs 2.91±0.46 μmol/L, P<0.05), and the patients with liver cancer also had a significantly higher level of plasma LPA than the normal population (4.99±0.55 μmol/L vs 1.61±0.39 μmol/L, P<0.05). The cell proliferation assay showed that LPA significantly promoted the proliferation of SMMC7721 cells, and cell proliferation rate increased with the increase in dose and time; in particular, the middle-and high-dose groups had a significantly higher proliferation rate than the control group (P<0.05). PTX inhibited the proliferative capacity of SMMC7721 cells in a time-dependent manner, and there was a significant difference between the groups (P<0.05). The proliferation rate of the 72-hour high-dose LPA group was 3.6 times that of the control group, while the proliferation rate of the PTX group was 0.6 times that of the control group; the proliferation rate of the 72-hour high-dose LPA+PTX group was 1.2 times that of the control group. In addition, LPA increased the migration ability of hepatoma cells, while PTX inhibited their migration, in a time-dependent manner, and there was a significant difference between the groups (P<0.05). The migration rate of the 72-hour high-dose LPA group was 3.09 times that of the control group, while the migration rate of the PTX group was 0.4 times that of the control group; the migration rate of the 72-hour high-dose LPA+PTX group was 0.99 times that of the control group. qPCR and Western blot showed that there were significant reductions in the mRNA and protein expression levels of P53 in SMMC7721 cells after LPA treatment, while there were significant increases in the mRNA and protein expression levels of FAK and RhoA; there was a significant difference between the LPA group and the control group (P<0.05). ConclusionThere is an abnormal increase in the expression of LPA in patients with liver cancer, and LPA can promote the proliferation of liver cancer cells and increase their migration ability. At the same time, LPA changes the expression levels of P53, FAK, and RhoA, which may be associated with the promotion of tumor development and progression by LPA.
10.P2X7/P2X4 Receptors Mediate Proliferation and Migration of Retinal Microglia in Experimental Glaucoma in Mice.
Meng-Xi XU ; Guo-Li ZHAO ; Xin HU ; Han ZHOU ; Shu-Ying LI ; Fang LI ; Yanying MIAO ; Bo LEI ; Zhongfeng WANG
Neuroscience Bulletin 2022;38(8):901-915
Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma. Here, we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension (COH). In COH retinas, the microglial proliferation that occurred was inhibited by the P2X7 receptor (P2X7R) blocker BBG or P2X7R knockout, but not by the P2X4R blocker 5-BDBD. Treatment of primary cultured microglia with BzATP, a P2X7R agonist, mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway. Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration, which was completely blocked by 5-BDBD. In vivo and in vitro experiments demonstrated that ATP, released from activated Müller cells through connexin43 hemichannels, acted on P2X7R to induce microglial proliferation, and acted on P2X4R/P2X7R (mainly P2X4R) to induce microglial migration. Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.
Adenosine Triphosphate/pharmacology*
;
Animals
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Cell Proliferation
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Glaucoma/metabolism*
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Mice
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Microglia/metabolism*
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Receptors, Purinergic P2X4/metabolism*
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Receptors, Purinergic P2X7/metabolism*
;
Retinal Ganglion Cells/metabolism*

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