Vasoactive intestinal peptide induces surfactant protein A expression in ATII cells through activation of PKC/c-Fos pathway

Vasoactive intestinal peptide (VIP) is a major neurotransmitter in the lungs and regulates many aspects of pulmonary functions. Pulmonary surfactant (PS), a complex mixture of lipids and proteins, produced by the alveolar type II (ATII) cells maintains alveolar integrity and plays important roles in the control of host defense and inflammation in the lungs. Surfactants deficiency or dysfunction is associated with occurrence and development of many pulmonary diseases. We reported previously that VIP enhanced the synthesis of pulmonary surfactants phospholipid in ATII cells. In this study, the effect of VIP on the expression of pulmonary surfactant protein A (SP-A) in lung explants was investigated. Firstly, we found that VIP elevated SP-A expression in ATII cells which was mediated by enhanced sp-a gene transcription. Furthermore, we identified that c-Fos protein was essential for VIP induced SP-A expression in ATII cells. Finally, we provided evidence to show that activation of c-Fos expression by PKC was required for VIP induced SP-A expression. Altogether, our work showed that VIP regulated the function of pulmonary surfactant system in the lungs and further investigation of the underlying mechanism would provide important clues for better therapeutic strategy design for pulmonary disorders caused by surfactant deficiency.

Research highlights▶ VIP elevates SP-A expression in ATII cells. ▶ C-Fos protein is essential for VIP induced SP-A expression in ATII cells. ▶ Activation of c-Fos expression by PKC is required for VIP induced SP-A expression.