BACKGROUND: Despite the presence of glucagon-like peptide-1 receptor (GLP-1R) in kidney tissues, its direct effect on diabetic nephropathy remains unclear. The transforming growth factor-β(1) (TGF-β(1)) and the connective tissue growth factor (CTGF) both induce extracellular matrix accumulation and persistent fibrosis in the glomerular mesangium of patients with diabetic nephropathy. OBJECTIVE: Herein, we demonstrate that a GLP-1R agonist, exendin-4, exerts renoprotective effects through its influence on TGF-β(1) and CTGF in human mesangial cells (HMCs), cultured in a high glucose medium. METHOD: HMCs, cultured in a high glucose medium, were used for the current study. The direct effect of exendin-4 on TGF-β(1) and CTGF expression was confirmed in HMCs. MDL-12330A (a specific adenylate cyclase inhibitor) and PKI14-22 (a protein kinase A inhibitor) were used to examine the role of the cAMP signaling pathway in exendin's anti-fibrosis action. RESULTS: The findings showed that exendin-4 inhibited the proliferation of HMCs, and upregulated the expression of TGF-β(1) and CTGF, induced by high glucose. The effect of exendin-4 is largely dependent on the activation of adenylate cyclase. CONCLUSION: This study provides new evidence that GLP-1 acts as an antifibrotic agent in HMCs.
BACKGROUND: Despite the presence of glucagon-like peptide-1 receptor (GLP-1R) in kidney tissues, its direct effect on diabetic nephropathy remains unclear. The transforming growth factor-β(1) (TGF-β(1)) and the connective tissue growth factor (CTGF) both induce extracellular matrix accumulation and persistent fibrosis in the glomerular mesangium of patients with diabetic nephropathy. OBJECTIVE: Herein, we demonstrate that a GLP-1R agonist, exendin-4, exerts renoprotective effects through its influence on TGF-β(1) and CTGF in human mesangial cells (HMCs), cultured in a high glucose medium. METHOD:HMCs, cultured in a high glucose medium, were used for the current study. The direct effect of exendin-4 on TGF-β(1) and CTGF expression was confirmed in HMCs. MDL-12330A (a specific adenylate cyclase inhibitor) and PKI14-22 (a protein kinase A inhibitor) were used to examine the role of the cAMP signaling pathway in exendin's anti-fibrosis action. RESULTS: The findings showed that exendin-4 inhibited the proliferation of HMCs, and upregulated the expression of TGF-β(1) and CTGF, induced by high glucose. The effect of exendin-4 is largely dependent on the activation of adenylate cyclase. CONCLUSION: This study provides new evidence that GLP-1 acts as an antifibrotic agent in HMCs.
Authors: Fernando Magdaleno; Chuck Christopher Blajszczak; Claudia Lisette Charles-Niño; Alma Marlene Guadrón-Llanos; Alan Omar Vázquez-Álvarez; Alejandra Guillermina Miranda-Díaz; Natalia Nieto; María Cristina Islas-Carbajal; Ana Rosa Rincón-Sánchez Journal: Exp Ther Med Date: 2019-08-20 Impact factor: 2.447
Authors: Sarika Chaudhari; Parisa Yazdizadeh Shotorbani; Yu Tao; Mark E Davis; Robert T Mallet; Rong Ma Journal: Am J Physiol Renal Physiol Date: 2020-05-11