Regulation of silicosis formation by lysophosphatidic acid and its receptors.

Abstract

Silicosis is a serious occupational disease characterized by lung fibrosis that is caused by long-term inhalation of silica-containing fine particles. Lysophosphatidic acid (LPA) and LPA1/3 plays a role in lung fibrosis. Until recently, there has been little research investigating the role of LPA and LPA receptors (LPAR) in silica-induced development of pulmonary fibrosis. In this study, we evaluated the hypothesis that LPA and LPA1/3 may play a role in silicosis pathogenesis using rat silicosis models induced by intratracheal instillation of silica, and randomly divided into control, silica, and VPC-12249 groups. LPA serum and bronchoalveolar lavage fluid (BALF) levels were quantified by ELISA. α-smooth muscle actin (α-SMA), type I and III collagen protein expression was quantified by western blotting (WB), and type I and III collagen mRNAs detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Lung hydroxyproline (HYP) levels were detected using alkaline hydrolysis, with hematoxylin and eosin (H&E) and picrosirius red staining used for pathological examination. In vitro experiments showed that LPA stimulated fibroblasts proliferated in a time and dose-dependent manner and promoted expression of α-SMA, and type I and III collagen. Moreover, LPA serum and BALF levels increased in silica-instilled rats. In vivo and in vitro experiments revealed that α-SMA expression and collagen deposition reduced significantly after VPC-12249 treatment, and histopathological results show VPC-12249 alleviates silicosis progression. In conclusion, our findings suggest that LPA promotes the proliferation, transformation, and collagen synthesis of fibroblasts, and that LPA-LPA1/3 are involved in the development of silicosis and may serve as novel therapeutic targets for treatment.

• Authors: Cuicui Cong, Lijun Mao, Yanlin Zhang, Zanmei Zhao, Xixian Xu, Jinyuan Zhao
• Journal: Experimental lung research (Exp Lung Res) Vol. 40 Issue 7 Pg. 317-26 (Sep 2014) ISSN: 1521-0499 [Electronic] England
• PMID: 24926730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Collagen Type I
• Collagen Type III
• Lysophospholipids
• Receptors, Lysophosphatidic Acid
• Silicon Dioxide
• lysophosphatidic acid

Topics

• Actins (metabolism)
• Animals
• Bronchoalveolar Lavage Fluid (chemistry)
• Cell Proliferation (drug effects, physiology)
• Collagen Type I (metabolism)
• Collagen Type III (metabolism)
• Fibroblasts (drug effects, metabolism)
• Humans
• Lung (drug effects, metabolism, pathology)
• Lysophospholipids (metabolism)
• Male
• Rats
• Rats, Sprague-Dawley
• Receptors, Lysophosphatidic Acid (metabolism)
• Silicon Dioxide (pharmacology)
• Silicosis (metabolism, pathology)