Sphingosine 1-Phosphate Receptors Negatively Regulate Collagen Type I/III Expression in Human Bone Marrow-derived Mesenchymal Stem Cell
Sphingosine 1-Phosphate Receptors Negatively Regulate Collagen Type I/III Expression in Human Bone Marrow-derived Mesenchymal Stem Cell
复制标题
1-磷酸鞘氨醇受体负调节人骨髓间充质干细胞中 I/III 型胶原蛋白的表达
DOI：
10.1002/jcb.24670
复制
发表时间：
2014-02-01
影响因子：
4
通讯作者：
Li, Liying
中科院分区：
文献类型：
--
作者：
Chang, Na;Xiu, Lei;Li, Liying
胶原蛋白是哺乳动物中含量最丰富的结构蛋白，在多种组织中都有表达。近年来，1-磷酸鞘氨醇受体(S1PR)被证明在胶原蛋白表达的调节中起着重要作用。我们以前的研究报道，S1PR通过上调小鼠骨髓间充质干细胞(BMSCs)中S1PR1/3的表达，参与了转化生长因子-1诱导的胶原表达，并导致实验性小鼠肝纤维化。但目前尚不清楚这一过程是否发生在人骨髓间充质干细胞(HMSCs)中。在本研究中，我们从细胞和分子水平提供了证据，证明S1PR1/3而不是S1PR2对hMSCs的胶原表达具有负性调节作用。我们发现，用转化生长因子-1处理人骨髓间充质干细胞后，胶原蛋白的表达呈剂量和时间依赖性上调。同时，转化生长因子-1以时间依赖的方式抑制hMSCs S1PR1/3的表达，但不抑制S1PR2的表达。此外，选择性下调S1PR1或沉默S1PR3均可诱导hMSCs表达I型和III型胶原。相反，siRNA抑制S1PR2对胶原蛋白的表达没有影响。综上所述，这些结果表明S1PR1和S1PR3对hMSCs中胶原蛋白的表达具有负调控作用。本研究强调了hMSCs与小鼠BMSCs的区别，为胶原蛋白的表达提供了一种新的调控机制，并指出了hMSCs在临床应用中的风险。J.细胞。生物化学。2014年，115：359-367。(C)2013年威利期刊公司。
Collagen is the most abundant structural protein in mammals and is expressed in various tissues. In recent years, sphingosine 1-phosphate receptors (S1PRs) have been proven to play an important role in the regulation of collagen expression. Our previous studies reported that S1PRs are involved in TGF-1-induced collagen expression via up-regulating S1PR1/3 in mouse bone marrow-derived mesenchymal stem cells (BMSCs), and result in experimental mouse liver fibrogenesis. But it remains unclear whether this process happens in human bone marrow-derived mesenchymal stem cells (hMSCs). In this study, we provide evidences that S1PR1/3, but not S1PR2, negatively regulate the expression of collagen in hMSCs using cellular and molecular approaches in vitro. We find that treatment of hMSCs with TGF-1 up-regulated collagen expression in a dose- and time-dependent manner. Meanwhile, TGF-1 inhibited the expression of S1PR1/3, but not S1PR2, in hMSCs in a time-dependent manner. Furthermore, either selective knock-down of S1PR1 or silencing S1PR3 induced collagen 1(I) and collagen 1(III) expression in hMSCs. In contrast, inhibition of S1PR2 by siRNA had no effects on the expression of collagen. Altogether, all these findings demonstrated that collagen expression was negatively regulated by S1PR1 and S1PR3 in hMSCs. This study highlights the differences between hMSCs and mouse BMSCs, provides a new regulation mechanism for collagen expression, and points out the risk of utilizing hMSCs in clinical applications. J. Cell. Biochem. 115: 359-367, 2014. (c) 2013 Wiley Periodicals, Inc.