Tang M, Zhong M, Shang Y, Lin H, Deng J, Jiang H, Lu H, Zhang Y, Zhang W
Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, PR China.
Cell Mol Life Sci. 2008 Sep;65(18):2924-32. doi: 10.1007/s00018-008-8255-3.
Advanced glycation end products (AGEs) play an important role in collagen deposition in diabetic cardiomyopathy. TRB3, a mammalian homolog of Drosophila tribbles, functions to increase glucose intolerance and regulates cell proliferation. We demonstrated that AGEs induce collagen type I expression but inhibit collagen type III expression, accompanied by increased TRB3 expression. Furthermore, the collagen type I induced byAGEs was down-regulated after inhibition of ERK and p38-MAPK, the collagen type III reduced by AGEs was up-regulated after inhibition of ERK. The expression of collagen types I and III regulated by AGEs through MAPK was partly reversed after treatment with TRB3 siRNA. It suggests that the TRB3/MAPK signaling pathway participates in the regulation of collagen types I and III by AGEs and may provide new therapeutic strategies for diabetic cardiomyopathy.
晚期糖基化终末产物（AGEs）在糖尿病性心肌病的胶原蛋白沉积中起重要作用。TRB3是果蝇tribbles的哺乳动物同源物，其作用是增加葡萄糖不耐受并调节细胞增殖。我们证明，AGEs诱导I型胶原蛋白表达，但抑制III型胶原蛋白表达，同时伴有TRB3表达增加。此外，抑制ERK和p38-MAPK后，AGEs诱导的I型胶原蛋白表达下调，抑制ERK后，AGEs降低的III型胶原蛋白表达上调。用TRB3 siRNA处理后，AGEs通过MAPK调节的I型和III型胶原蛋白表达部分逆转。这表明TRB3/MAPK信号通路参与AGEs对I型和III型胶原蛋白的调节，可能为糖尿病性心肌病提供新的治疗策略。
