1.Mechanism of acupuncture for chronic blunt injury of lumbar muscle based on IGF-1/PI3K/AKT pathway.
Qun CHEN ; Dongmei WANG ; Zhengyu YANG ; Xiulian ZHENG ; Jianping LIN ; Shaoqing CHEN
Chinese Acupuncture & Moxibustion 2025;45(12):1759-1769
OBJECTIVE:
To explore the effect and mechanism of acupuncture at "Weizhong" (BL40) on microcirculation of paravertebral skeletal muscle in rats with chronic blunt injury of lumbar muscle based on the insulin-like growth factor-1 (IGF-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.
METHODS:
Forty-eight SPF-grade SD rats were randomized into a blank group (8 rats) and a modeling group (40 rats). Chronic blunt injury model was established by weight impact method in the modeling group. Forty rats were successfully modeled, and were randomly divided into a model group, an acupuncture at Weizhong group (Weizhong group), an acupuncture at non-acupoint group (non-acupoint group), an inhibitor group, and an inhibitor+acupuncture at Weizhong group (inhibitor+Weizhong group), 8 rats in each group. In the Weizhong group and the inhibitor+Weizhong group, acupuncture was applied at bilateral "Weizhong" (BL40). In the non-acupoint group, acupuncture was applied at non-acupoints, i.e. points 0.5 cm inward from bilateral "Weizhong" (BL40). The acupuncture intervention was delivered 20 min each time, once a day for continuous 2 weeks. In the inhibitor group and the inhibitor+Weizhong group, intraperitoneal injection of IGF-1 receptor (IGF-1R) inhibitor was given once a day, at a dosage of 2 mg/100 g, for continuous 2 weeks. Before modeling and on the 1st, 7th and 14th days of intervention, the body mass was measured. Before and after modeling, and after intervention, the limb grip strength and paw withdrawal threshold (PWT) were measured. After intervention, the morphology of psoas muscle was observed by HE staining; the ultrastructure of psoas muscle capillaries was observed by electron microscopy; the levels of serum vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) were detected by ELISA; and the protein and mRNA expression of IGF-1, IGF-1R, PI3K, AKT of psoas muscle was detected by Western blot and real-time PCR.
RESULTS:
Compared with the blank group, in the model group, the body mass on the 7th and 14th days of intervention, the limb grip strength, and the PWT of left and right hind feet were decreased (<i>Pi><0.001, <i>Pi><0.01); the skeletal muscle cells showed enlarged intercellular space, loosely arranged and irregularly shaped, the capillaries in the psoas muscle tissues were edematous, and the lumen of the blood vessels was obviously atrophied; the levels of serum VEGF and eNOS were decreased (<i>Pi><0.001); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K, p-AKT/AKT values were decreased (<i>Pi><0.001), the mRNA expression of IGF-1, IGF-1R, PI3K and AKT was decreased (<i>Pi><0.001, <i>Pi><0.05). Compared with the model group, in the Weizhong group, the body weight was increased on the 7th and 14th days of intervention (<i>Pi><0.001), the limb grip strength and the PWT of the left and right hind feet were increased (<i>Pi><0.001, <i>Pi><0.01); the arrangement of the skeletal muscle cells was relatively tight and the intercellular space was reduced, the blood vessels tended to be regular and the structure of the basement membrane was continuous, while the lumens of blood vessels were collapsed locally; the levels of serum VEGF and eNOS were increased (<i>Pi><0.001); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K, p-AKT/AKT values were increased (<i>Pi><0.001), the mRNA expression of IGF-1, IGF-1R, PI3K and AKT was increased (<i>Pi><0.001, <i>Pi><0.01). Compared with the model group, in the inhibitor group, the body mass was decreased on the 7th and 14th days of intervention (<i>Pi><0.05, <i>Pi><0.01); the limb grip strength and the PWT of the left hind foot were decreased (<i>Pi><0.01, <i>Pi><0.001); the intercellular space of skeletal muscle cells was larger, the nuclei of the cells and erythrocytes were scattered in the intercellular space, the damage of the capillaries in the muscular tissues was serious, the collagen fibers were sparsely distributed and disorganized; the levels of serum VEGF and eNOS were decreased (<i>Pi><0.001, <i>Pi><0.01); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K and p-AKT/AKT values were decreased (<i>Pi><0.01, <i>Pi><0.05, <i>Pi><0.001), the mRNA expression of IGF-1, IGF-1R, PI3K, and AKT was decreased (<i>Pi><0.01, <i>Pi><0.001, <i>Pi><0.05). Compared with the Weizhong group, in the non-acupoint group and the inhibitor+Weizhong group, the body mass was decreased on the 7th and 14th days of intervention (<i>Pi><0.001, <i>Pi><0.01), the limb grip strength was decreased (<i>Pi><0.001); the morphology of muscle cell was relatively poor, with generally irregular, there was mild collapse and atrophy in the vascular lumen, and mild edema in the endothelial cells; the levels of serum VEGF and eNOS were decreased (<i>Pi><0.001); in psoas muscle, the protein expression of IGF-1 and IGF-1R, as well as the p-PI3K/PI3K and p-AKT/AKT values were decreased (<i>Pi><0.01, <i>Pi><0.001), the mRNA expression of IGF-1, IGF-1R, PI3K, and AKT was decreased (<i>Pi><0.001, <i>Pi><0.01, <i>Pi><0.05). Compared with the Weizhong group, the PWT of the left hind foot was decreased in the non-acupoint group (<i>Pi><0.001), and PWT of the left and right hind feet was decreased in the inhibitor+Weizhong group (<i>Pi><0.001).
CONCLUSION
Acupuncture at "Weizhong" (BL40) promotes lumbar muscle repair in chronic low back pain, its mechanism may be related to the activation of the IGF-1/PI3K/AKT pathway, thereby improving the microcirculation.
Animals
;
Insulin-Like Growth Factor I/genetics*
;
Acupuncture Therapy
;
Rats, Sprague-Dawley
;
Rats
;
Proto-Oncogene Proteins c-akt/genetics*
;
Male
;
Humans
;
Muscle, Skeletal/metabolism*
;
Signal Transduction
;
Phosphatidylinositol 3-Kinases/genetics*
;
Wounds, Nonpenetrating/metabolism*
;
Acupuncture Points
2.Recent advances in the mechanism of insulin-like growth factor-1-mediated exercise-induced improvement of skeletal muscle atrophy.
Qian WANG ; Yi-Min HE ; Yu-Mo DONG ; Hua-Duo WU ; Yi ZHANG ; Ning JIANG
Acta Physiologica Sinica 2025;77(5):969-978
Skeletal muscle atrophy is characterized by a reduction in both the size and quantity of skeletal muscle fibers, resulting in impaired muscle strength and function. It mainly includes disuse muscle atrophy, aging muscle atrophy, denervated muscle atrophy and muscle atrophy caused by disease <i>etci>. As a cost-effective way, exercise has been widely used in the prevention and treatment of skeletal muscle atrophy, but its mechanism for improving skeletal muscle atrophy remains unclear. Recent studies have indicated that insulin-like growth factor 1 (IGF-1) plays an important role in improving muscle atrophy through exercise, in addition to promoting the survival of neurons, lowering blood sugar, and anti-inflammation. This article reviews recent findings on the mechanisms by which IGF-1 mediates exercise-induced improvement in skeletal muscle atrophy, providing a theoretical basis for the prevention and treatment of this disease.
Insulin-Like Growth Factor I/physiology*
;
Muscular Atrophy/therapy*
;
Humans
;
Exercise/physiology*
;
Muscle, Skeletal
;
Animals
;
Insulin-Like Peptides
3.Peak growth hormone and insulin-like growth factor 1 levels in girls with isolated premature thelarche and their predictive value for central precocious puberty.
Jie CHEN ; Kun-Di WANG ; Rong HUANG ; Shu-Fang LIU ; Qi YANG ; Li YANG
Chinese Journal of Contemporary Pediatrics 2025;27(11):1360-1366
OBJECTIVES:
To compare serum insulin-like growth factor 1 (IGF-1) and peak growth hormone (GH) levels between girls with isolated premature thelarche (IPT) and central precocious puberty (CPP), to construct a prediction model for progression from IPT to CPP, and to assess its diagnostic value.
METHODS:
Girls diagnosed with IPT (<i>ni>=111) between January 2022 and August 2023 at the China-Japan Friendship Hospital and the Xinjiang Production and Construction Corps Hospital were retrospectively included. According to follow-up outcomes, participants were categorized into a CPP group (35 cases) and an IPT group (36 cases). A clinical prediction model for progression to CPP was constructed by multivariable logistic regression, and the contributions of IGF-1 and peak GH were evaluated. Restricted cubic spline analysis was used to assess the dose-response relationships of IGF-1 and peak GH with CPP. Decision curve analysis was applied to evaluate clinical utility.
RESULTS:
IGF-1 and peak GH were higher in the CPP group than in the IPT group (<i>Pi><0.05). Compared with model 1 (without IGF-1 and peak GH), model 2 (with IGF-1 and peak GH) showed significantly higher area under the curve, integrated discrimination improvement, and net reclassification improvement (all <i>Pi><0.05). Model 2 (χ 2=6.054, <i>Pi>=0.889) also demonstrated better goodness-of-fit than model 1 (χ 2=7.717, <i>Pi>=0.634). Nonlinear dose-response relationships were observed for peak GH and IGF-1 with CPP (<i>Pi> for overall trend <0.05; <i>Pi> for nonlinearity <0.05). Decision curve analysis indicated that combined prediction using IGF-1 and peak GH provided greater net benefit than either biomarker alone.
CONCLUSIONS
Peak GH and IGF-1 are closely associated with progression from IPT to CPP in girls. A clinical prediction model incorporating peak GH and IGF-1 can improve prediction of progression to CPP and yield higher net benefit.
Humans
;
Female
;
Puberty, Precocious/etiology*
;
Insulin-Like Growth Factor I/analysis*
;
Child
;
Retrospective Studies
;
Human Growth Hormone/blood*
;
Predictive Value of Tests
;
Child, Preschool
;
Logistic Models
4.Advances in pharmacological research for retinopathy of prematurity.
Yanxi XIE ; Suilian ZHENG ; Hui YANG
Journal of Zhejiang University. Medical sciences 2025;54(3):411-421
Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease that threatens the vision of premature infants. Various novel drugs have demonstrated therapeutic potential for ROP by targeting signaling pathways associated with vascular endothelial growth factor (VEGF) [such as PI3K/AKT, hypoxia-inducible factor (HIF)-1α/VEGF], oxidative stress, tumor necrosis factor (TNF)-α, and Notch pathways. Propranolol, insulin-like growth factor-1, and celecoxib attenuate pathological neovascularization via the PI3K/Akt signaling pathway. Tripterine and melatonin inhibit retinal neovascularization by modulating the HIF-1α/VEGF signaling axis. Adiponectin mitigates the damage caused by oxidative stress and preserves endothelial function by enhancing endothelial nitric oxide synthase activity. Omega-3 polyunsaturated fatty acids suppress TNF-α-mediated inflammatory responses, modulate retinal development and angiogenesis, and reduce retinal neovascular lesions. DAPT, a γ-secretase inhibitor, blocks Notch signaling to suppress abnormal vascular proliferation. These agents exhibit synergistic multi-pathway anti-angiogenic effects in preclinical models and early-phase clinical trials, offering critical insights for advancing drug development and clinical translation in ROP management.
Retinopathy of Prematurity/metabolism*
;
Humans
;
Signal Transduction/drug effects*
;
Infant, Newborn
;
Vascular Endothelial Growth Factor A/metabolism*
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Tumor Necrosis Factor-alpha/metabolism*
;
Oxidative Stress/drug effects*
;
Fatty Acids, Omega-3/therapeutic use*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Receptors, Notch/metabolism*
;
Angiogenesis Inhibitors/therapeutic use*
;
Insulin-Like Growth Factor I/therapeutic use*
5.Therapeutic effect of concentrated growth factors combined with self-curing calcium phosphate cement on periodontal intrabony defects: Clinical and radiographic evaluation.
Xinying WANG ; Xueyuan CHENG ; Yong ZHANG ; Fei LI ; Jinyu DUAN ; Jing QIAO
Journal of Peking University(Health Sciences) 2025;57(1):42-50
OBJECTIVE:
To clarify the role of concentrated growth factors (CGF) in the treatment of periodontal cement defects using calcium phosphate cement (CPC) with self-curing properties.
METHODS:
Thirty-six intrabony defects were randomly divided into two groups. The experimental group received CGF+CPC treatment (<i>ni>=18), while the control group received CPC treatment alone (<i>ni>=18). The probing depth, clinical attachment loss, and hard tissue filling as measured by cone beam CT (CBCT) were evaluated at baseline and 1 year postoperatively in both groups, and the levels of major growth factors in CGF and serum were compared [platelet-derived growth factor-BB (PDGF-BB), transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF)].
RESULTS:
At baseline, there were no statistically significant differences in probing depth, clinical attachment loss and CBCT measurements between the two groups (<i>Pi>>0.05). At 1 year postoperatively, significant improvements were observed in parameters mentioned above in both groups (<i>Pi> < 0.05). The CGF+CPC group seemed more effective compared with the CPC group in reduction of probing depth [(4.5±1.3) mm <i>vs.i> (3.2±1.1) mm] and clinical attachment gain [(3.8±0.9) mm <i>vs.i> (2.0±0.5) mm, <i>Pi> < 0.05]. Compared with the group treated with CPC alone, the hard tissue filling degree shown by CBCT in the CGF+CPC group was significantly increased [the reduction of the depth of the intrabony defects was (3.9±1.2) mm <i>vs.i> (2.1±0.7) mm, respectively, <i>Pi> < 0.01]. At 1 year post-operatively, the volume of the intrabony defects shown by CBCT in the CGF+CPC group was reduced by (0.031 8±0.004 1) mL, which was significantly more than that in the CPC group [(0.019 7±0.001 2) mL, <i>Pi> < 0.05]. In addition, the concentration of the main growth factors (PDGF-BB, TGF-β1, IGF-1, and VEGF) in CGF were higher than those in serum (<i>Pi> < 0.001).
CONCLUSION
After 1 year of follow-up, the results of the present study indicated that CGF could significantly improve the clinical and radiological effects of CPC on the treatment of periodontal intrabony defects.
Humans
;
Calcium Phosphates/therapeutic use*
;
Male
;
Female
;
Bone Cements/therapeutic use*
;
Middle Aged
;
Cone-Beam Computed Tomography
;
Alveolar Bone Loss/therapy*
;
Becaplermin
;
Adult
;
Insulin-Like Growth Factor I
;
Intercellular Signaling Peptides and Proteins/therapeutic use*
;
Proto-Oncogene Proteins c-sis/blood*
;
Transforming Growth Factor beta1/blood*
;
Vascular Endothelial Growth Factor A/blood*
6.Abnormal elevation of growth hormone in patients with pituitary adenoma combined with cirrhosis: A case report.
Yanlei WANG ; Min DUAN ; Jianzhong XIAO ; Wenhui ZHAO
Journal of Peking University(Health Sciences) 2025;57(2):400-402
The oral glucose growth hormone suppression test is commonly used in the clinical diagnosis of acromegaly, but its results can be influenced by a variety of factors. This case report discusses a patient with a pituitary tumor and concurrent liver cirrhosis, highlighting the complexities in interpreting test results under such conditions. The patient, a 54-year-old male, presented with blurred vision as his primary complaint. Notably, the physical examination revealed no changes in facial features, no enlargement of hands or feet, and no other symptoms typically associated with acromegaly, which might otherwise suggest excessive growth hormone activity. Magnetic Resonance Imaging (MRI) of the pituitary gland indicated that the gland was within normal size parameters, but a small low-intensity lesion mea-suring approximately 3 mm×2 mm identified. This finding was consistent with a pituitary microadenoma. The patient's fasting growth hormone levels were significantly elevated at 8.470 μg/L, compared with the normal range of less than 2.47 μg/L. Conversely, fasting insulin-like growth factor-1 (IGF-1) levels were notably low, recorded at 41 and 52 μg/L, whereas the normal range for a person of his age was between 87 and 234 μg/L. Other pituitary hormones, including those regulating the thyroid, adrenal cortex, and sex hormones, were found to be within normal ranges. Despite this, during the glucose growth hormone suppression test, an abnormal elevation of growth hormone was observed. To investigate further, the patient was administered branched-chain amino acids, and the suppression test was repeated. However, the abnormal elevation of growth hormone persisted, indicating a failure to normalize the response. Given the patient's lack of clinical signs typically associated with elevated growth hormone secretion, the history of liver cirrhosis became a significant consideration. The disparity between elevated growth hormone levels and reduced IGF-1 levels suggested that the pituitary lesion was a non-functional adenoma rather than a source of excess hormone production. Consequently, it was concluded that the abnormal response of growth hormone to the glucose suppression test was likely related to the patient's liver cirrhosis. In addition to chronic liver disease, various other conditions could influence the results of the oral glucose tolerance growth hormone suppression test. According to the literature, factors such as puberty, diabetes, anorexia nervosa, and protein malnutrition could also affect test outcomes. These conditions could cause similar abnormalities in growth hormone dynamics, complicating the diagnosis. Therefore, clinicians must be vigilant and consider these potential influences when interpreting test results.For an accurate diagnosis of acromegaly, it is essential to combine clinical symptoms, detailed medical history, and imaging studies. The presence of conditions like liver cirrhosis should prompt careful interpretation of the test results, ensuring that other contributing factors are not overlooked. This comprehensive approach is crucial to avoid misdiagnosis and to ensure that appropriate treatment strategies are implemented based on a thorough understanding of the patient's overall health status.
Humans
;
Male
;
Middle Aged
;
Pituitary Neoplasms/blood*
;
Liver Cirrhosis/blood*
;
Adenoma/blood*
;
Human Growth Hormone/blood*
;
Insulin-Like Growth Factor I/metabolism*
;
Acromegaly/etiology*
;
Magnetic Resonance Imaging
7.Triptolide Ameliorates Collagen-Induced Arthritis and Bleomycin-Induced Pulmonary Fibrosis in Rats by Suppressing IGF1-Mediated Epithelial Mesenchymal Transition.
Pei-Pei LU ; Lan YAN ; Qi GENG ; Lin LIN ; Lu-Lu ZHANG ; Chang-Qi SHI ; Peng-Cheng ZHAO ; Xiao-Meng ZHANG ; Jian-Yu SHI ; Cheng LYU
Chinese journal of integrative medicine 2025;31(12):1069-1077
OBJECTIVE:
To investigate the common mechanisms among collagen-induced arthritis (CIA), bleomycin (BLM)-induced pulmonary fibrosis, and CIA+BLM to evaluate the therapeutic effect of triptolide (TP) on CIA+BLM.
METHODS:
Thirty-six male Sprague-Dawley rats were randomly assigned to 6 groups according to a random number table (n=6 per group): normal control (NC), CIA, BLM, combined CIA+BLM model, TP low-dose (TP-L, 0.0931 mg/kg), and TP high-dose (TP-H, 0.1862 mg/kg) groups. The CIA model was induced by intradermal injection at the base of the tail with emulsion of bovine type II collagen and incomplete Freund's adjuvant (1:1), with 200 µL administered on day 0 and a booster of 100 µL on day 7. Pulmonary fibrosis was induced via a single intratracheal injection of BLM (5 mg/kg). The CIA+BLM model combined both protocols, and TP was administered orally from day 14 to 35. After successful modeling, arthritis scores were recorded every 3 days, and pulmonary function was assessed once at the end of the treatment period. Lung tissues were collected for histological analysis (hematoxylin eosin and Masson staining), immunohistochemistry, measurement of hydroxyproline (HYP) content, and calculation of lung coefficient. In addition, HE staining was performed on the ankle joint. Total RNA was extracted from lung tissues for transcriptomic analysis. Differentially expressed genes (DEGs) were compared with those from the RA-associated interstitial lung diseases patient dataset GSE199152 to identify overlapping genes, which were then used to construct a protein-protein interaction network. Hub genes were identified using multiple topological algorithms.
RESULTS:
The successfully established CIA+BLM rat model exhibited significantly increased arthritis scores and severe pulmonary fibrosis (P<0.01). By intersecting the DEGs obtained from transcriptomic analysis of lung tissues in CIA, BLM, and CIA+BLM rats with DEGs from rheumatoid arthritis-interstitial lung disease patients (GSE199152 dataset), 50 upregulated and 44 downregulated genes were identified. Through integrated PPI network analysis using multiple topological algorithms, IGF1 was identified as a central hub gene. TP intervention significantly improved pulmonary function by increasing peak inspiratory flow (P<0.01), and reduced lung index and HYP content (P<0.01). Histopathological analysis showed that TP alleviated alveolar collapse, interstitial thickening, and collagen deposition in the lung tissues (P<0.01). Moreover, TP treatment reduced the expression of collagen type I and α-SMA and increased E-cadherin levels (P<0.01). TP also significantly reduced arthritis scores and ameliorated synovial inflammation (P<0.05). Both transcriptomic and immunohistochemical analyses confirmed that IGF1 expression was elevated in the CIA+BLM group and downregulated following TP treatment (P<0.05).
CONCLUSION
TP exerts protective effects in the CIA+BLM model by alleviating arthritis and pulmonary fibrosis through the inhibition of IGF1-mediated EMT.
Animals
;
Pulmonary Fibrosis/complications*
;
Bleomycin/adverse effects*
;
Phenanthrenes/pharmacology*
;
Male
;
Rats, Sprague-Dawley
;
Diterpenes/pharmacology*
;
Epoxy Compounds/therapeutic use*
;
Arthritis, Experimental/complications*
;
Insulin-Like Growth Factor I/metabolism*
;
Rats
;
Lung/physiopathology*
8.Correlation between waist circumference and IGF-1 levels in an elderly population in Bali, Indonesia
I Made Pande Dwipayana ; Wira Gotera ; Made Ratna Saraswati ; I Made Siswadi Semadi ; Ida Bagus Aditya Nugraha ; Ketut Suastika ; Anak Agung Gde Budhiarta ; Padma Amrita ; Wahyu Pratama Putra
Journal of the ASEAN Federation of Endocrine Societies 2024;39(2):9-12
Background:
Hyperinsulinemia due to insulin resistance is hypothesized to act as a promotor of cancer growth. In addition to the direct effects of hyperinsulinemia on cancer cells, the stimulation of tumor cell growth can also be indirectly mediated through growth factors and receptors such as insulin-like growth factor 1 (IGF-1). Increased cancer risk is also associated with increased adipose tissue, such as in abdominal obesity, due to the higher risk of insulin resistance and hyperinsulinemia. Waist circumference is a parameter that indicates an individual's level of adiposity. In addition, the risk of cancer also increases in the elderly as they age. This study aims to assess the correlation between waist circumference and IGF-1 levels in the elderly population in Bali, Indonesia.
Methodology:
This study used a cross-sectional analytical design conducted in the Melinggih Village, Gianyar Regency. The study was conducted in September 2023. This study has been approved by the Research Ethics Commission number 2020/UN14.2.2.VII.14/LT/2023. The study population included elderly individuals residing in the Melinggih Village who were willing to participate. Data analysis encompassed descriptive analysis and the Spearman correlation test.
Result:
A total of 88 subjects participated in the study, consisting of 57 females (64.8%) and 31 males (35.2%). A statistically significant but weak correlation coexists between waist circumference and IGF-1 levels.
Conclusion
A weak but statistically significant positive correlation was found between waist circumference and IGF-1 levels in the elderly. However, because of the small sample size, another study with a bigger sample size with enough power to investigate this association needs to be done to validate the results of the current study.
Elderly
;
Aged
;
IGF-1
;
Insulin-Like Growth Factor I
;
Waist Circumference
9.Research progress on molecular mechanism related to skeletal muscle atrophy.
Yi-Bing KE ; Dawuti ABUDOUKEREMU ; Hao-Ran GUO ; Yong-Ping WANG
Acta Physiologica Sinica 2024;76(6):1056-1068
The maintenance of skeletal muscle quality involves various signal pathways that interact with each other. Under normal physiological conditions, these intersecting signal pathways regulate and coordinate the hypertrophy and atrophy of skeletal muscles, balancing the protein synthesis and degradation of muscle. When the total rate of protein synthesis exceeds that of protein degradation, the muscle gradually becomes enlarged, while when the total rate of protein synthesis is lower than that of protein degradation, the muscle shrinks. Myocyte atrophy mainly involves two protein degradation pathways, namely ubiquitin-proteasome and autophagy-lysosome. Protein degradation pathway is activated during muscle atrophy, resulting in the loss of muscle mass. Muscle atrophy can occur under various conditions such as malnutrition, aging and cachexia. Skeletal muscle atrophy caused by orthopedic diseases mainly includes disuse muscular atrophy caused by fracture and denervation muscular atrophy. The signal pathways that control and coordinate protein synthesis and degradation in skeletal muscle include insulin-like growth factor 1 (IGF1)-Akt-mammalian target of rapamycin (mTOR), myostatin-activin A-Smad, G protein α inhibitory peptide 2 (Gαi2)-PKC, nuclear factor κB (NF-κB), ectodysplasin A2 receptor (EDA2R)-NF-κB inducing kinase (NIK) and mitogen-activated protein kinase (MAPK) pathways. This paper provides a comprehensive review of the protein degradation pathways in skeletal muscle atrophy and the associated signal pathways regulating protein degradation in muscular atrophy.
Humans
;
Muscular Atrophy/etiology*
;
Muscle, Skeletal/pathology*
;
Signal Transduction
;
Animals
;
Insulin-Like Growth Factor I/metabolism*
;
Myostatin/physiology*
;
TOR Serine-Threonine Kinases/metabolism*
;
Autophagy/physiology*
;
NF-kappa B/metabolism*
;
Proteolysis
;
Proteasome Endopeptidase Complex/physiology*
10.Correlation between serum ghrelin and liver-expressed antimicrobial peptide-2 with idiopathic short stature in children.
Qing LIU ; Wei-Chun ZHANG ; Bo CHEN ; Ya-Wen SONG
Chinese Journal of Contemporary Pediatrics 2024;26(12):1261-1266
OBJECTIVES:
To investigate the expression levels of ghrelin and liver-expressed antimicrobial peptide-2 (LEAP-2) in children with idiopathic short stature (ISS) to provide reference for further understanding the etiology of short stature.
METHODS:
A prospective study was conducted from December 2021 to October 2023, involving 46 children diagnosed with ISS (ISS group) and 46 healthy children with normal height (control group) at the First Affiliated Hospital of Shihezi University. General data and serum levels of ghrelin and LEAP-2 were compared between the two groups. The predictive value of these two indicators for ISS was evaluated using receiver operating characteristic (ROC) curve analysis.
RESULTS:
The serum level of ghrelin in the ISS group was higher than that in the control group, while the level of LEAP-2 was lower (<i>Pi><0.05). The ratio of LEAP-2 to ghrelin was lower in the ISS group compared to the control group (<i>Pi><0.05). Multivariate logistic regression analysis showed that HtSDS, IGF-1, ghrelin, LEAP-2, and the ratio of LEAP-2/ghrelin were independently associated with the occurrence of ISS (<i>Pi><0.05). ROC curve analysis indicated that the AUCs for ghrelin, LEAP-2, the ratio of ghrelin to LEAP-2, and their combination in predicting ISS were all >0.8. The optimal cutoff values for ghrelin, LEAP-2, and the LEAP-2/ghrelin ratio were 5 607 pg/mL, 1 155 pg/mL, and 0.212, respectively. In children with ISS, ghrelin showed a negative correlation with chronological age, LEAP-2, and the LEAP-2/ghrelin ratio (<i>Pi><0.05), while it was positively correlated with growth rate and peak growth hormone levels (<i>Pi><0.05). LEAP-2 was negatively correlated with growth rate, peak growth hormone levels, and ghrelin (<i>Pi><0.05), but positively correlated with chronological age and the LEAP-2/ghrelin ratio (<i>Pi><0.05).
CONCLUSIONS
Ghrelin and LEAP-2 are correlated with the occurrence of ISS, which may provide references for the diagnosis and etiological analysis of children with ISS.
Humans
;
Ghrelin/blood*
;
Male
;
Child
;
Female
;
Prospective Studies
;
Child, Preschool
;
Growth Disorders/etiology*
;
Antimicrobial Cationic Peptides/blood*
;
Body Height
;
Adolescent
;
Insulin-Like Growth Factor I/analysis*
;
Blood Proteins


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