TGF-β1-induced transdifferentiation of derma fibroblasts into myofibroblasts: A study of mechanism
- Author:
Jie XIONG
1
Author Information
1. Department of Burns
- Publication Type:Journal Article
- Keywords:
Fibroblast;
Knockout;
Mice;
Myofibroblast;
Smad3;
Transdifferentiation;
Transforming growth factor beta
- From:
Academic Journal of Second Military Medical University
2010;28(11):1175-1179
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the possible pathways and regulatory mechanism of TGF-β1-induced transdifferentiation of derma fibroblasts(FB) into myofibroblasts. Methods: Mice Wild-type and Smad3 knockout(Smad3 KO) derma FB were divided into 9 groups, namely, A: Wild-type FB; B:Wild-type FB+TGF-β1; C:Wild-type FB+SB431542; D:Wild-type FB+SB431542 +TGF-β1; E:Smad3 KO FB; F:Smad3 KO FB+TGF-β1; G:Wild-type FB+SB203580+TGF-β1; H:Wild-type FB+PD98059 +TGF-β1; and I: Wild-type FB + SP600125+TGF-β1. After synchronization treatment, the cells were treated with TGF-β1 with or without pretreatment with above mentioned kinases inhibitors. Then the cells were collected for RNA extraction and the expression of α-SMA was detected by real time quantitative RT PCR; some cells were analyzed by single cell RT-PCR to test the positive expression rate of α-SMA. Results: The expression and positive rate of α-SMA in SB431542 group and Smad3 knockout group were significantly increased(group E vs. group A; group D vs. group C; group F vs. group E, P<0.01) and those in SP600125 group and SB203580 group were significantly inhibited (group G and I vs. group B,P<0.05). Conclusion: In TGF-β1-induced derma fibroblasts transdifferentiation into myofibroblasts, Smad3 pathway plays a negative regulatory role and p38/ MAPK and JNK/MAPK pathway play a positive regulatory role.
