ALK5 抑制可阻断 TGFβ 诱导的人包皮成纤维细胞中 CCN1 的表达。
ALK5 inhibition blocks TGFβ-induced CCN1 expression in human foreskin fibroblasts.
机构信息
Department of Dentistry, University of Western Ontario, London, ON, Canada, N6A 5C1.
出版信息
J Cell Commun Signal. 2014 Mar;8(1):59-63. doi: 10.1007/s12079-014-0229-7. Epub 2014 Feb 25.
Abstract
The potent profibrotic cytokine TGFβ induces connective tissue growth factor (CCN2/CTGF) is induced in fibroblasts in a fashion sensitive to SB-431542, a specific pharmacological inhibitor of TGFβ type I receptor (ALK5). In several cell types, TGFβ induces CCN1 but suppresses CCN3, which opposes CCN1/CCN2 activities. However, whether SB-431542 alters TGFβ-induced CCN1 or CCN3 in human foreskin fibroblasts in unclear. Here we show that TGFβ induces CCN1 but suppresses CCN3 expression in human foreskin fibroblasts in a SB-431542-sensitive fashion. These results emphasize that CCN1/CCN2 and CCN3 are reciprocally regulated and support the notion that blocking ALK5 or addition of CCN3 may be useful anti-fibrotic approaches.
摘要
有效促进纤维化的细胞因子 TGFβ可诱导成纤维细胞产生结缔组织生长因子（CCN2/CTGF），这种诱导作用对 TGFβ Ⅰ型受体（ALK5）的特异性药理学抑制剂 SB-431542 敏感。在几种细胞类型中，TGFβ 诱导 CCN1 但抑制 CCN3，CCN3 与 CCN1/CCN2 的活性相反。然而，SB-431542 是否会改变人包皮成纤维细胞中 TGFβ 诱导的 CCN1 或 CCN3 尚不清楚。在这里，我们发现 TGFβ 以 SB-431542 敏感的方式诱导人包皮成纤维细胞中 CCN1 的表达，但抑制 CCN3 的表达。这些结果强调了 CCN1/CCN2 和 CCN3 是相互调节的，并支持阻断 ALK5 或添加 CCN3 可能是一种有用的抗纤维化方法的观点。
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