Differential regulation of collagen types I and III expression in cardiac fibroblasts by AGEs through TRB3/MAPK signaling pathway
Differential regulation of collagen types I and III expression in cardiac fibroblasts by AGEs through TRB3/MAPK signaling pathway
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DOI：
10.1007/s00018-008-8255-3
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发表时间：
2008-09-01
影响因子：
8
通讯作者：
Zhang, W.
中科院分区：
文献类型：
--
作者：
Tang, M.;Zhong, M.;Zhang, W.
糖基化终末产物（AGEs）在糖尿病心肌病胶原沉积中起重要作用。TRB 3是果蝇tribbles的哺乳动物同源物，其功能是增加葡萄糖耐受不良并调节细胞增殖。我们证明，AGEs诱导I型胶原蛋白的表达，但抑制III型胶原蛋白的表达，伴随着增加TRB 3的表达。抑制ERK和p38-MAPK后，AGEs诱导的I型胶原表达下调，抑制ERK后，AGEs诱导的III型胶原表达上调。TRB 3 siRNA可部分逆转AGEs通过MAPK调控的I型和III型胶原的表达。提示TRB 3/MAPK信号通路参与AGEs对I型和III型胶原的调节，可能为糖尿病心肌病的治疗提供新的策略。
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.