{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:33:55Z","timestamp":1792701235871,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Idiopathic pulmonary fibrosis is a devastating disease characterized by alveolar epithelial cell injury, the accumulation of fibroblasts\/myofibroblasts, and the deposition of extracellular matrix proteins. Lysophosphatidic acid (LPA) signaling through its G protein\u2013coupled receptors is critical for its various biological functions. Recently, LPA and LPA receptor 1 were implicated in lung fibrogenesis. However, the role of other LPA receptors in fibrosis remains unclear. Here, we use a bleomycin-induced pulmonary fibrosis model to investigate the roles of LPA2 in pulmonary fibrogenesis. In the present study, we found that LPA2 knockout (Lpar2\u2212\/\u2212) mice were protected against bleomycin-induced lung injury, fibrosis, and mortality, compared with wild-type control mice. Furthermore, LPA2 deficiency attenuated the bleomycin-induced expression of fibronectin (FN), \u03b1\u2013smooth muscle actin (\u03b1-SMA), and collagen in lung tissue, as well as levels of IL-6, transforming growth factor\u2013\u03b2 (TGF-\u03b2), and total protein in bronchoalveolar lavage fluid. In human lung fibroblasts, the knockdown of LPA2 attenuated the LPA-induced expression of TGF-\u03b21 and the differentiation of lung fibroblasts to myofibroblasts, resulting in the decreased expression of FN, \u03b1-SMA, and collagen, as well as decreased activation of extracellular regulated kinase 1\/2, Akt, Smad3, and p38 mitogen-activated protein kinase. Moreover, the knockdown of LPA2 with small interfering RNA also mitigated the TGF-\u03b21\u2013induced differentiation of lung fibroblasts. In addition, LPA2 deficiency significantly attenuated the bleomycin-induced apoptosis of alveolar and bronchial epithelial cells in the mouse lung. Together, our data indicate that the knockdown of LPA2 attenuated bleomycin-induced lung injury and pulmonary fibrosis, and this may be related to an inhibition of the LPA-induced expression of TGF-\u03b2 and the activation and differentiation of fibroblasts.<\/jats:p>","DOI":"10.1165\/rcmb.2013-0070oc","type":"journal-article","created":{"date-parts":[[2013,6,28]],"date-time":"2013-06-28T14:56:56Z","timestamp":1372431416000},"page":"912-922","source":"Crossref","is-referenced-by-count":101,"title":["Lysophosphatidic Acid Receptor\u20132 Deficiency Confers Protection against Bleomycin-Induced Lung Injury and Fibrosis in Mice"],"prefix":"10.1093","volume":"49","author":[{"given":"Long Shuang","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pharmacology"},{"name":"Institute for Personalized Respiratory Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panfeng","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology"},{"name":"Institute for Personalized Respiratory Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anantha","family":"Harijith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjiao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Illinois Institute of Technology, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe G. 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