机械压应力通过TGF-β1通路治疗增生性瘢痕的分子机制研究
申宽宏, 黄东, 吴伟炽, 黄永军, 牟勇
中国临床解剖学杂志 ›› 2013, Vol. 31 ›› Issue (3) : 299-302.
机械压应力通过TGF-β1通路治疗增生性瘢痕的分子机制研究
Study on the molecular mechanism of mechanical compression treating hyperplastic scar via TGF-β 1 pathway
目的 通过机械压应力系统干预增生性瘢痕成纤维细胞,研究皮肤创伤后增生性瘢痕组织中TGF-β1通路中TGF-β1受体、smads和胶原蛋白的差异性表达,探究压应力治疗增生性瘢痕的分子机制。 方法 体外培养增生性瘢痕细胞,应用RT-PCR方法比较机械性压应力干预组和空白对照组增生性瘢痕成纤维细胞内Smad3、Smad7和胶原蛋白表达差异。 结果 根据RT-PCR结果,增生性瘢痕成纤维细胞系中在机械性压应力干预后,TGF-β1受体表达量增高,Smad3、 Smad7、CollagenⅠ表达量下降,差异有统计学意义(P<0.05),collagenⅢ表达两组差异无统计学意义(P>0.05)。 结论 机械压应力治疗增生性瘢痕可通过TGF-β1通路中抑制Smad3的表达从而促进胶原蛋白Ⅰ的降解。
Objective To study the effects of mechanical compression on the expression of TGF-β1 receptor,smads and collagen from human skin hypertrophic scar fibroblast via the mechanical pressure system intervention, and explore the potential molecular mechanism of pressure treatment of hyperplastic scar. Methods Hypertrophic scar cells were cultured in vitro ,the expression of TGF-β1 receptor,Smad3,Smad7 and collagens were determined on mRNA level by RT-PCR; Difference in expression between the mechanical pressure intervention experimental group and the control group in the hypertrophic scar fibroblasts was tested. Results The RT - PCR results indicated that the expression of smad3 and smad7, Collagen Ⅰ was reduced after pressure treatment the difference being statistically significant (P<0.05), whereas the expression of TGF-β1 receptor increased, the difference being statistically significant (P<0.05). Conclusion Mechanical compression can inhibit Smad3 expression and promote TGF-β1 receptor expression so as to promote the degradation of hyperplastic scar collagen.
增生性瘢痕 / 成纤维细胞 / 机械压应力 / 胶原蛋白 / 转化生长因子-&beta
Hypertrophic scar / Fibroblast / Mechanical compression / TGF-β / Collagen
[1] Hu M, Sabelman EE, Cao Y, et al. Three-dimensional hyaluronic acid grafts promote healing and reduce scar formation in skin incision wounds
[J]. J Biomed Mater Res B Appl Biomater,2003,67(1):586-592.
[2] Shah R, Rahaman B, Hurley CK, et al. Allelic diversity in the TGFB1 regulatory region: characterization of novel functional single nucleotide polymorphisms
[J]. Hum Genet, 2006, 119(1-2):61-74.
[3] Fujiwara M, Muragaki Y, Ooshima A. Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration
[J]. Br J Dermatol, 2005, 153(2):295-300.
[4] Yu H, Bock O, Bayat A, et al. Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring
[J]. J Plast Reconstr Aesthet Surg, 2006, 59(3):221-229.
[5] Hu M, Sabelman EE, Cao Y, et al. Three-dimensional hyaluronic acid grafts promote healing and reduce scar formation in skin incision wounds
[J]. J Biomed Mater Res B Appl Biomater, 2003, 67(1):586-592.
[6] Chin GS, Liu W, Peled Z, et al. Differential expression of transforming growth factor-beta receptors I and II and activation of Smad 3 in keloid fibroblasts
[J]. Plast Reconstr Surg, 2001,108(2):423-429.
[7] Yuan W, Varga J. Transforming growth factor-beta repression of matrix metalloproteinase-1 in dermal fibroblasts involves Smad3
[J]. J Biol Chem, 2001, 276(42):38502-38510.
[8] 胡庆柳,朴英杰. 转化生长因子β及其生物学效应
[J]. 生物学通报, 2000, 35(9):18-20.
[9] Dong C, Li Z, Alvarez RJ, et al. Microtubule binding to Smads may regulate TGF beta activity
[J]. Mol Cell, 2000, 5(1):27-34.
[10] Schiller M, Javelaud D, Mauviel A. TGF-beta-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing
[J]. J Dermatol Sci, 2004, 35(2):83-92.
[11] 陈伟,付小兵,孙同柱,等. 增生瘢痕中转化生长因子基因的表达
[J]. 中华外科杂志, 2002,40(1):17-19.
[12] Inagaki Y, Mamura M, Kanamaru Y, et al. Constitutive phosphorylation and nuclear localization of Smad3 are correlated with increased collagen gene transcription in activated hepatic stellate cells
[J]. J Cell Physiol, 2001, 187(1):117-123.
[13] Saika S, Yamanaka O, Nishikawa-Ishida I, et al. Effect of Smad7 gene overexpression on transforming growth factor beta-induced retinal pigment fibrosis in a proliferative vitreoretinopathy mouse model
[J]. Arch Ophthalmol, 2007, 125(5):647-654.
[14] Balestrini JL, Billiar KL. Equibiaxial cyclic stretch stimulates fibroblasts to rapidly remodel fibrin
[J]. J Biomech, 2006, 39(16):2983-2990.
[15] Ramtani S. Mechanical modelling of cell/ECM and cell/cell interactions during the contraction of a fibroblast-populated collagen microsphere: theory and model simulation
[J]. J Biomech, 2004, 37(11):1709-1718.
国家自然科学基金(81071564)
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