微小RNA-10a和微小RNA-181c通过靶向纤溶酶原激活物抑制剂-1和尿激酶型纤溶酶原激活物来调节增生性瘢痕中I型胶原蛋白的生成。

MiR-10a and miR-181c regulate collagen type I generation in hypertrophic scars by targeting PAI-1 and uPA.

作者信息

Li Chao, Zhu Hua-Yu, Bai Wen-Dong, Su Lin-Lin, Liu Jia-Qi, Cai Wei-Xia, Zhao Bin, Gao Jian-Xin, Han Shi-Chao, Li Jun, Hu Da-Hai

机构信息

Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.

Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.

出版信息

FEBS Lett. 2015 Jan 30;589(3):380-9. doi: 10.1016/j.febslet.2014.12.024. Epub 2014 Dec 29.

DOI:10.1016/j.febslet.2014.12.024

PMID:25554417

Abstract

Urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been proposed to play key roles in extracellular matrix (ECM) deposition in hypertrophic scars (HS). Here, we found that in HS fibroblasts (HFs) miR-181c and miR-10a were differentially-expressed and targeted uPA and PAI-1, respectively. The production of Type 1 collagen (Col1) was inhibited by miR-181c knockdown or miR-10a overexpression in HFs, and this resulted in increased levels of metalloproteinase 1 (MMP1). These results suggest that the miR-181c-uPA and miR-10a-PAI-1 regulatory pathways have an integral role in HS pathogenesis.

摘要

尿激酶型纤溶酶原激活剂（uPA）和纤溶酶原激活剂抑制剂-1（PAI-1）被认为在增生性瘢痕（HS）的细胞外基质（ECM）沉积中起关键作用。在此，我们发现，在HS成纤维细胞（HFs）中，miR-181c和miR-10a表达存在差异，且分别靶向uPA和PAI-1。在HFs中，miR-181c敲低或miR-10a过表达可抑制I型胶原蛋白（Col1）的产生，这导致金属蛋白酶1（MMP1）水平升高。这些结果表明，miR-181c-uPA和miR-10a-PAI-1调控途径在HS发病机制中起不可或缺的作用。