BioSpace Collaborative

Academic/Biomedical Research
News & Jobs
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

Free Newsletters
My Subscriptions

News by Subject
News by Disease
News by Date
Search News
Post Your News

Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Pharm Country
  Bio NC
  Southern Pharm
  BioCanada East
  C2C Services & Suppliers™


Company Profiles

Research Store

Research Events
Post an Event
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Immunology - Molecular Biology - Physiology - Respiratory Medicine

A New Antifibrotic Target of Ac-SDKP: Inhibition of Myofibroblast Differentiation in Rat Lung with Silicosis
Published: Tuesday, July 03, 2012
Author: Hong Xu et al.

by Hong Xu, Fang Yang, Ying Sun, Yuan Yuan, Hua Cheng, Zhongqiu Wei, Shuyu Li, Tan Cheng, Darrell Brann, Ruimin Wang


Myofibroblast differentiation, characterized by a-smooth muscle actin (a-SMA) expression, is a key process in organ fibrosis, and is induced by TGF-ß. Here we examined whether an anti-fibrotic agent, N-acetyl-seryl-aspartyl-lysylproline (Ac-SDKP), can regulate induction of TGF-ß signaling and myofibroblast differentiation as a potential key component of its anti-fibrotic mechanism in vivo and in vitro.

Methodology/Principal Findings

Rat pulmonary fibroblasts were cultured in vitro and divided to 4 groups 1) control; 2) TGF-ß1; 3) TGF-ß1+ LY364947; 4) TGF-ß1+Ac-SDKP. For in vivo studies, six groups of animals were utilized 1) control 4w; 2) silicotic 4w; 3) control 8w; 4) silicotic 8w; 5) Ac-SDKP post-treatment; 6)Ac-SDKP pre-treatment. SiO2 powders were douched in the trachea of rat to make the silicotic model. Myofibroblast differentiation was measured by examining expression of a-SMA, as well as expression of serum response factor (SRF), a key regulator of myofibroblast differentiation. The expressions of collagen, TGF-ß1 and RAS signaling were also assessed. The results revealed that TGF-ß1 strongly induced myofibroblast differentiation and collagen synthesis in vitro, and that pre-treatment with Ac-SDKP markedly attenuated myofibroblast activation, as well as induction of TGF-ß1 and its receptor. Similar results were observed in vivo in the pathologically relevant rat model of silicosis. Ac-SDKP treatment in vivo strongly attenuated 1) silicosis-induced increased expressions of TGF-ß1 and RAS signaling, 2) myofibroblast differentiation as indicated by a robust decrease of SRF and a-SMA-positive myofibroblast localization in siliconic nodules in the lung, 3) collagen deposition.


The results of the present study suggest a novel mechanism of action for Ac-SDKP’s beneficial effect in silicosis, which involves attenuation of TGF-ß1 and its receptors, SRF and Ang II type 1 receptor (AT1) expression, collagen deposition and myofibroblast differentiation. The results further suggest that therapies targeting myofibroblast differentiation may have therapeutic efficacy in treatment of silicosis of the lung.