Connective tissue growth factor and IGF-I are produced by human renal fibroblasts and cooperate in the induction of collagen production by high glucose
Connective tissue growth factor and IGF-I are produced by human renal fibroblasts and cooperate in the induction of collagen production by high glucose
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DOI：
10.2337/diabetes.52.12.2975
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发表时间：
2003-12-01
期刊：
影响因子：
7.7
通讯作者：
van Kooten, C
中科院分区：
文献类型：
--
作者：
Lam, S;van der Geest, RN;van Kooten, C
肾小管间质纤维化是糖尿病肾病发展的重要组成部分。各种肾细胞类型，包括成纤维细胞，有助于肾脏中的过度基质沉积。虽然转化生长因子-β（TGF-β）被认为在纤维化过程中起主要作用，但其他生长因子也参与其中。在这里，我们研究了结缔组织生长因子（CTGF）和IGF-I对人肾成纤维细胞I型和III型胶原蛋白的产生及其参与葡萄糖诱导的基质积累的影响。我们已经证明，在高血糖条件下，在TGF-β信号传导缺失的情况下，肾成纤维细胞中CTGF和IGF-I的表达均增加。虽然CTGF单独对胶原分泌没有影响，但与IGF-I联合刺激可增强胶原积累。此外，IGF-I还与葡萄糖对胶原的诱导具有协同作用。此外，我们观察到中和性抗CTGF抗体对葡萄糖诱导的胶原蛋白分泌有部分抑制作用，从而首次证明内源性CTGF参与了人肾成纤维细胞中葡萄糖诱导的作用。因此，CTGF和IGF-I的协同作用可能参与了葡萄糖诱导的肾小管间质纤维化中基质的积聚，并可能参与了糖尿病肾病的发病机制。
Tubulointerstitial fibrosis is an important component in the development of diabetic nephropathy. Various renal cell types, including fibroblasts, contribute to the excessive matrix deposition in the kidney. Although transforming growth factor-beta (TGF-beta) has been thought to play a major role during fibrosis, other growth factors are also involved. Here we examined the effects of connective tissue growth factor (CTGF) and IGF-I on collagen type I and III production by human renal fibroblasts and their involvement in glucose-induced matrix accumulation. We have demonstrated that both CTGF and IGF-I expressions were increased in renal fibroblasts under hyperglycemic conditions, also in the absence of TGF-beta signaling. Although CTGF alone had no effect on collagen secretion, combined stimulation with IGF-I enhanced collagen accumulation. Furthermore, IGF-I also had a synergistic effect with glucose on the induction of collagens. Moreover, we observed a partial inhibition in glucose-induced collagen secretion with neutralizing anti-CTGF antibodies, thereby demonstrating for the first time the involvement of endogenous CTGF in glucose-induced effects in human renal fibroblasts. Therefore, the cooperation between CTGF and IGF-I might be involved in glucose-induced matrix accumulation in tubulointerstitial fibrosis and might contribute to the pathogenesis of diabetic nephropathy.