Alpha-melanocyte stimulating hormone suppresses the proliferation of human Tenon's capsule fibroblast proliferation induced by transforming growth factor beta 1

作者：Zhang, Zheng^*; Ma, Jin; Yao, Ke; Yin, Jinfu

来源：Molecular Biology, 2012, 46(4): 563-568.

DOI：10.1134/S0026893312040140

• alpha-melanocyte stimulating hormone
• human Tenon's capsule fibroblast
• transforming growth factor beta 1

Alpha-melanocyte stimulating hormone (alpha-MSH) is a proopiomelanocortin derivative and a multi-function neuropeptide, well know for its pigment-inducing capacity, inhibitory action on proinflammatory cytokines and chemoattractant cytokines, and suppressive action on collagen synthesis. Human Tenon's capsule fibroblasts (HTF) are the main effector cells in the initiation and mediation of wound healing and fibrotic scar formation after trabeculectomy. In this study effects of alpha-MSH on proliferation of HTF stimulated by transforming growth factor beta 1 (TGF-beta 1), have been investigated and discussed. Fibroblasts were cultured in Dulbecco's modified Eagle's medium (DMEM) in the control group, and in DMEM with TGF-beta 1 at concentration of 10(-12) M the TGF-beta 1 group, and DMEM with 10(-12) M TGF-beta 1 and alpha-MSH ranging from 0, 10(-8) to 10(-4) M in the TGF-beta 1/alpha-MSH groups. Cell proliferation was assessed 48 h later by the CellTiter 96 Aqueous One Solution Cell Proliferation Assay. After administration of TGF-beta 1 at a concentration of 10(-12) M, or TGF-beta 1 at 10(-12) M plus alpha-MSH at 10(-6) M, the mRNA level of type I (alpha 1) collagen, fibronectin, TNF-alpha, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), MMP-1, MMP-2, TIMP-1, and TIMP-2 in HTF were analyzed using the real time reverse transcription polymerase chain reaction. alpha-MSH demonstrated an inhibitory effect on the proliferation of HTF induced by TGF-beta 1 in a dose-dependent manner, when the concentration was lower than 10(-5) M, and a suppressive effect on the mRNA of type I (alpha 1) collagen, TNF-alpha, ICAM-1 and VCAM-1, which were up-regulated by TGF-beta 1. results showed a reverse effect of alpha-MSH on the imbalance between MMPs and TIMPs with TGF-beta 1. Based on all these results, we conclude that alpha-MSH could effectively suppress we conclude that alpha-MSH could effectively suppress HTF proliferation and modulate correlative genes in collagen synthesis stimulated by TGF-beta 1, which implies that alpha-MSH could be exploited in the treatment of conjunctival fibrotic scar disorder.

• 出版日期2012-7
• 单位浙江大学