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Journal of Biosciences

, Volume 40, Issue 5, pp 855–862 | Cite as

Semaphorin 4A enhances lung fibrosis through activation of Akt via PlexinD1 receptor

  • Hai-Ying Peng
  • Wei Gao
  • Fa-Rong Chong
  • Hong-Yan Liu
  • Ji ZhangEmail author
Article

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 α-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 fibrotic 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.

Keywords

Akt signalling fibrosis lung fibroblast PlexinD1 Semaphorin 4A 

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Copyright information

© Indian Academy of Sciences 2015

Authors and Affiliations

  • Hai-Ying Peng
    • 1
  • Wei Gao
    • 1
  • Fa-Rong Chong
    • 2
  • Hong-Yan Liu
    • 3
  • Ji Zhang
    • 4
    Email author
  1. 1.Department of Clinical Laboratory MedicineLinyi People’s HospitalLinyiChina
  2. 2.Department of Pediatric SurgeryLinyi People’s HospitalLinyiChina
  3. 3.Department of EndocrinologyLinyi People’s HospitalLinyiChina
  4. 4.Department of Thoracic Surgery and Lung Transplantation CenterWuxi People’s Hospital Affiliated to Nanjing Medical UniversityWuxiChina

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