Effect of peroxisome proliferators-activated receptor gamma agonist on phenotypic transition of adventitia fibroblasts induced by transforming growth factor beta 1 in vitro

Shaojun MA; Wenwei CAI; Jing SHENG

ABSTRACT

BACKGROUND:

Previous studies demonstrated that adventitia fibroblasts exhibit important role in the hyperplasia of newly born endomembrane after blood vessel injury. However, the mechanism regarding phenotypic transition of adventitia fibroblasts in vitro remains unclear.

OBJECTIVE:

To observe effect of peroxisome proliferators-activated receptor ?agonist (PPAR ?) on phenotypic transition of adventitia fibroblasts induced by transforming growth factor ?1 (TGF-?1) in vitro, as well as the expression of collagen protein Ⅰ. DESIGN, TIME AND

SETTING:

A randomized grouping control experiment was performed at the Tissue Engineering Laboratory of Ninth Affiliated Hospital of Shanghai Jiao Tong Medical College between July 2007 and October 2008. MATERIALS The aorta thoracica's adventitial fibroblasts were cultured from Sprague Dawley rats, with 2-month-old, weighing 120 g. The TGF-?1 was supplied by American GenWay Biotech Company. The rosiglitazone power was purchased from Beijing Comens Chemical Co., Ltd.

METHODS:

The experiment was divided into 3 groups In the TGF-?1 group, fibroblasts was induced with TGF-?1 with different concentrations (3, 5, 10, 15 ?g/L) for 48 hours; in the rosiglitazone group, fibroblasts was induced with rosiglitazone (5, 10, 30, 50 ?mol/L) for 45 minutes followed by co-culture with 10 ?g/L TGF-?1 for 48 hours. There was no intervention measure in the control group. MAIN OUTCOME

MEASURES:

The phenotypic transition of fibroblasts was measured by ?-smooth muscle actin, the expression of smooth muscle ? 2-actin, as well as collagen type Ⅰ was determined by protein immunoblotting.

RESULTS:

Compared with the control group, 5 ?g/L TGF-?1 could significantly stimulate the changes of phenotypic transition of fibroblasts as well as the expression of smooth muscle ?2-actin and collagen type Ⅰ, which reach a peak level when treated with 10 ?g/L TGF-?1 (P 0.05). Compared with control group, 30 ?mol/L rosiglitazone could significantly inhibit changes of phenotypic transition of fibroblasts as well as the expression of smooth muscle ? 2-actin and collagen type Ⅰ(P