AIM:To explore the dynamic change of focal adhesion kinase (FAK) in renal tissues of rats with type 2 diabetes mellitus (T2DM), and to investigate its role in the pathogenesis of diabetic nephropathy (DN). METHODS:The rat model of T2DM was established and the diabetic rats were randomly divided into 8-week DM (DM8), 12-week DM (DM12) and 16-week DM (DM16) groups. Meanwhile, normal control (NC) and high-fat high-sucrose control (HC) groups were also established. The protein expression of FAK, transforming growth factor β1 (TGF-β1), extracellular signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2 and fibronectin (FN) was detected by immunohistochemical staining. The protein levels of FAK and p-FAK (Tyr397) were detected by Western blotting. The mRNA level of FAK in the renal cortex was examined by RT-PCR. RESULTS:The expression of FAK protein in renal tubular epithelial cells in DM12 and DM16 groups was significantly higher than that in NC, HC and DM8 groups (P<0.05). Moreover, TGF-β1, p-ERK1/2 and FN protein expression in DM groups was significantly increased compared with NC and HC groups (P<0.05). The levels of FAK and p-FAK (Tyr397) in the renal cortex in DM12 and DM16 groups were significantly up-regulated compared with NC, HC and DM8 groups (P<0.05), and the expression trend of p-FAK in different groups was in accordance with that of total FAK. The FAK protein expression was positively correlated with the expression of TGF-β1, p-ERK1/2 and FN proteins (P<0.01). Compared with NC, HC and DM8 groups, the expression of FAK mRNA increased remarkably in DM12 and DM16 groups (P<0.05). CONCLUSION: There is a possibility that FAK is activated as a downstream effector of TGF-β1 in T2DM, which enhances the expression of FN protein through activating ERK1/2, and therefore plays an important role in the pathogenesis of type 2 diabetic nephropathy.
李霜,王圆圆,刘丽荣,石磊,石明隽,肖瑛,张国忠,郭兵. 黏着斑激酶在2型糖尿病大鼠肾组织中的表达变化及意义[J]. 中国病理生理杂志, 2013, 29(8): 1400-1405.
LI Shuang, WANG Yuan-yuan, LIU Li-rong, SHI Lei, SHI Ming-jun, XIAO Ying, ZHANG Guo-zhong, GUO Bing. Role of focal adhesion kinase expression in renal tissues of type 2 diabetic rats. Chin J Pathophysiol, 2013, 29(8): 1400-1405.