Lysophosphatidic Acid Receptor–2 Deficiency Confers Protection against Bleomycin-Induced Lung Injury and Fibrosis in Mice

• DOI: 10.1165/rcmb.2013-0070oc
• Publication Date: 2013-06-28T18:56:56Z
• Authors: Long Shuang Huang; Panfeng Fu; Priya Patel; Anantha Harijith; Tianjiao Sun; Yutong Zhao; Joe G. N. Garcia; Jerold Chun; Viswanathan Natar...
• Keywords: Myofibroblast

Idiopathic pulmonary fibrosis is a devastating disease characterized by alveolar epithelial cell injury, the accumulation of fibroblasts/myofibroblasts, and deposition extracellular matrix proteins. Lysophosphatidic acid (LPA) signaling through its G protein-coupled receptors critical for various biological functions. Recently, LPA receptor 1 were implicated in lung fibrogenesis. However, role other remains unclear. Here, we use bleomycin-induced model to investigate roles LPA2 In present study, found that knockout (Lpar2(-/-)) mice protected against fibrosis, mortality, compared with wild-type control mice. Furthermore, deficiency attenuated expression fibronectin (FN), α-smooth muscle actin (α-SMA), collagen tissue, as well levels IL-6, transforming growth factor-β (TGF-β), total protein bronchoalveolar lavage fluid. human fibroblasts, knockdown LPA-induced TGF-β1 differentiation fibroblasts myofibroblasts, resulting decreased FN, α-SMA, collagen, activation regulated kinase 1/2, Akt, Smad3, p38 mitogen-activated kinase. Moreover, small interfering RNA also mitigated TGF-β1-induced fibroblasts. addition, significantly apoptosis bronchial cells mouse lung. Together, our data indicate injury this may be related an inhibition TGF-β