scholarly journals The Effect of CHIR 99021, a Glycogen Synthase Kinase-3β Inhibitor, on Transforming Growth Factor β-Induced Tenon Fibrosis

2021 ◽  
Vol 62 (15) ◽  
pp. 25
Author(s):  
Sang Yeop Lee ◽  
Min Kyoung Chae ◽  
Jin Sook Yoon ◽  
Chan Yun Kim
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Glycogen Synthase ◽  
Transforming Growth Factor Β ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β

scholarly journals Glycogen Synthase Kinase-3β is Involved in the Process of Myocardial Hypertrophy Stimulated by Insulin-Like Growth Factor-1

2004 ◽  
Vol 68 (3) ◽  
pp. 247-253 ◽  
Author(s):  
Satomi-Kobayashi Seimi ◽  
Kawashima Seinosuke ◽  
Sakoda Tsuyoshi ◽  
Ueyama Tomomi ◽  
Hirase Tetsuaki ◽  
...  
Keyword(s):  
Growth Factor ◽  
Myocardial Hypertrophy ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Insulin Like Growth Factor ◽  
Glycogen Synthase Kinase 3Β

scholarly journals Functional Effects of PTPN11 (SHP2) Mutations Causing LEOPARD Syndrome on Epidermal Growth Factor-Induced Phosphoinositide 3-Kinase/AKT/Glycogen Synthase Kinase 3β Signaling

2010 ◽  
Vol 30 (10) ◽  
pp. 2498-2507 ◽  
Author(s):  
Thomas Edouard ◽  
Jean-Philippe Combier ◽  
Audrey Nédélec ◽  
Sophie Bel-Vialar ◽  
Mélanie Métrich ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Hek293 Cells ◽  
Glycogen Synthase Kinase 3Β ◽  
Leopard Syndrome ◽  
Epidermal Growth ◽  
Gsk 3Β ◽  
Phosphoinositide 3 Kinase

ABSTRACT LEOPARD syndrome (LS), a disorder with multiple developmental abnormalities, is mainly due to mutations that impair the activity of the tyrosine phosphatase SHP2 (PTPN11). How these alterations cause the disease remains unknown. We report here that fibroblasts isolated from LS patients displayed stronger epidermal growth factor (EGF)-induced phosphorylation of both AKT and glycogen synthase kinase 3β (GSK-3β) than fibroblasts from control patients. Similar results were obtained in HEK293 cells expressing LS mutants of SHP2. We found that the GAB1/phosphoinositide 3-kinase (PI3K) complex was more abundant in fibroblasts from LS than control subjects and that both AKT and GSK-3β hyperphosphorylation were prevented by reducing GAB1 expression or by overexpressing a GAB1 mutant unable to bind to PI3K. Consistently, purified recombinant LS mutants failed to dephosphorylate GAB1 PI3K-binding sites. These mutants induced PI3K-dependent increase in cell size in a model of chicken embryo cardiac explants and in transcriptional activity of the atrial natriuretic factor (ANF) gene in neonate rat cardiomyocytes. In conclusion, SHP2 mutations causing LS facilitate EGF-induced PI3K/AKT/GSK-3β stimulation through impaired GAB1 dephosphorylation, resulting in deregulation of a novel signaling pathway that could be involved in LS pathology.

scholarly journals Chronic treatment with the mitochondrial peptide humanin prevents age-related myocardial fibrosis in mice

2018 ◽  
Vol 315 (5) ◽  
pp. H1127-H1136 ◽  
Author(s):  
Qing Qin ◽  
Hemal Mehta ◽  
Kelvin Yen ◽  
Gerardo Navarrete ◽  
Sebastian Brandhorst ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Myocardial Fibrosis ◽  
Cardiac Fibrosis ◽  
Biological Process ◽  
Glycogen Synthase ◽  
Myocardial Dysfunction ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Aged Mice

Cardiac fibrosis is a biological process that increases with age and contributes to myocardial dysfunction. Humanin (HN) is an endogenous mitochondria-derived peptide that has cytoprotective effects and reduces oxidative stress. The present study aimed to test the hypothesis that chronic supplementation of exogenous HN in middle-aged mice could prevent and reverse cardiac fibrosis and apoptosis in the aging heart. Female C57BL/6N mice at 18 mo of age received 14-mo intraperitoneal injections of vehicle (old group; n = 6) or HN analog (HNG; 4 mg/kg 2 times/wk, old + HNG group, n = 8) and were euthanized at 32 mo of age. C57BL/6N female mice (young group, n = 5) at 5 mo of age were used as young controls. HNG treatment significantly increased the ratio of cardiomyocytes to fibroblasts in aging hearts, as shown by the percentage of each cell type in randomly chosen fields after immunofluorescence staining. Furthermore, the increased collagen deposition in aged hearts was significantly reduced after HNG treatment, as indicated by picrosirius red staining. HNG treatment also reduced in aging mice cardiac fibroblast proliferation (5′-bromo-2-deoxyuridine staining) and attenuated transforming growth factor-β1, fibroblast growth factor-2, and matrix metalloproteinase-2 expression (immunohistochemistry or real-time PCR). Myocardial apoptosis was inhibited in HNG-treated aged mice (TUNEL staining). To decipher the pathway involved in the attenuation of the myocardial fibrosis by HNG, Western blot analysis was done and showed that HNG upregulated the Akt/glycogen synthase kinase -3β pathway in aged mice. Exogenous HNG treatment attenuated myocardial fibrosis and apoptosis in aged mice. The results of the present study suggest a role for the mitochondria-derived peptide HN in the cardioprotection associated with aging. NEW & NOTEWORTHY Cardiac fibrosis is a biological process that increases with age and contributes to myocardial dysfunction. Humanin is an endogenous mitochondria-derived peptide that has cytoprotective effects and reduces oxidative stress. Here, we demonstrate, for the first time, that exogenous humanin treatment attenuated myocardial fibrosis and apoptosis in aging mice. We also detected upregulated Akt/glycogen synthase kinase-3β pathway in humanin analog-treated mice, which might be the mechanism involved in the cardioprotective effect of humanin analog in aging mice.

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