Li Wenbin, Cui Meiyu, Wei Yong, Kong Xianglei, Tang Lijun, Xu Dongmei
Renal Division, Department of Medicine, Shandong Provincial Qianfoshan Hospital, Jinan City.
Cell Physiol Biochem. 2012;30(3):749-57. doi: 10.1159/000341454. Epub 2012 Aug 2.
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.
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.
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.
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.
This study provides new evidence that GLP-1 acts as an antifibrotic agent in HMCs.
尽管肾组织中存在胰高血糖素样肽-1受体（GLP-1R），但其对糖尿病肾病的直接作用仍不清楚。转化生长因子-β(1)（TGF-β(1)）和结缔组织生长因子（CTGF）均能诱导糖尿病肾病患者肾小球系膜细胞外基质积聚和持续性纤维化。
在此，我们证明一种GLP-1R激动剂艾塞那肽-4通过影响高糖培养基中培养的人系膜细胞（HMCs）中的TGF-β(1)和CTGF发挥肾脏保护作用。
本研究使用在高糖培养基中培养的HMCs。在HMCs中证实了艾塞那肽-4对TGF-β(1)和CTGF表达的直接作用。使用MDL-12330A（一种特异性腺苷酸环化酶抑制剂）和PKI14-22（一种蛋白激酶A抑制剂）来研究cAMP信号通路在艾塞那肽抗纤维化作用中的作用。
研究结果表明，艾塞那肽-4抑制HMCs的增殖，并上调高糖诱导的TGF-β(1)和CTGF的表达。艾塞那肽-4的作用很大程度上依赖于腺苷酸环化酶的激活。
本研究提供了新的证据，表明GLP-1在HMCs中作为一种抗纤维化剂发挥作用。
