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    • Keywords


      Akt signalling; fibrosis; lung fibroblast; PlexinD1; Semaphorin 4A

    • Abstract


      Semaphorin 4A plays a regulatory role in immune function and angiogenesis. However, its specific involvement in controlling lung fibrosis, a process that is closely related to angiogenesis and inflammation is still poorly understood. In the present study, we show that treatment of Sema4A on normal lung fibroblasts induces expression of proteins that contribute to a contractile phenotype, including a-smooth muscle actin (𝛼-SMA), ezrin, moesin, and paxillin. We confirm that Sema4A enhances the ability of lung fibroblasts to contract collagen gel. Sema4A treatment led to resistance to apoptosis in normal lung fibroblasts. Relative to normal lung fibroblasts, fibroblasts cultured from scars of patients with the flbrotic disease Systemic Sclerosis (SSc) showed elevated Sema4A secretion, enhanced 𝛼-SMA, ezrin, moesin, and paxillin expression, and high ability to induce collagen gel contraction. Using neutralizing antibody against Sema4A receptor, PlexinD1, we found that endogenous Sema4A signalling in SSc fibroblast was through PlexinD1 receptor. We then identified the signalling mechanism through which Sema4A-PlexinD1 promotes the ability of normal fibroblasts to contract a collagen gel matrix. Western blot analysis showed that Sema4A activated the Akt pathway in lung fibroblasts, and the specific inhibitor of Akt pathway, Akt inhibitor III, blocked the ability of Sema4A to promote the ability of lung fibroblasts to contract a collagen gel matrix. Thus, blocking Sema4A-PlexinD1-Akt cascades might be beneficial in reducing pulmonary fibrosis.

    • Author Affiliations


      Hai-Ying Peng1 Wei Gao1 Fa-Rong Chong2 Hong-Yan Liu3 Ji Zhang4

      1. Department of Clinical Laboratory Medicine, Linyi People's Hospital, Linyi, Shandong 276003, China
      2. Department of Pediatric Surgery, Linyi People s Hospital, Linyi, Shandong 276003, China
      3. Department of Endocrinology, Linyi People's Hospital, Linyi, Shandong 276003, China
      4. Department of Thoracic Surgery and Lung Transplantation Center, Wuxi People s Hospital Afjiliated to Nanjing Medical Universi, Wuxi, Jiangsu 214123, China
    • Dates

  • Journal of Biosciences | News

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      Posted on July 25, 2019

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