title: The neuropeptide catestatin promotes vascular smooth muscle cell proliferation through the Ca2+-calcineurin-NFAT signaling pathway.
abstract: The Chromogranin A-derived neuropeptide catestatin is an endogenous nicotinic cholinergic antagonist that acts as a pleiotropic hormone. Since catestatin shares several functions with other members derived from the chromogranin/secretogranin protein family and other neuropeptides which exert proliferative effects on vascular smooth muscle cells (VSMCs), we therefore hypothesized that catestatin would regulate VSMC proliferation. The present study demonstrates that catestatin caused a dose-dependent induction of proliferation in rat aortic smooth muscle cells and furthermore evoked a sustained increase in intracellular calcium. This subsequently leaded to enhanced activation of the Ca(2+)/calmodulin-dependent phosphatase, calcineurin and resulted in an activation of the Ca(2+)-dependent transcription factor, nuclear factor of activated T cells (NFAT), initiating transcription of proliferative genes. In addition, cyclosporin A (CsA), a potent inhibitor of calcineurin, abrogated catestatin-mediated effect on VSMCs, indicating that the calcineurin-NFAT signaling is strongly required for catestatin-induced growth of VSMCs. The present study establishes catestatin as a novel proliferative cytokine on vascular smooth muscle cells and this effect is mediated by the Ca(2+)-calcineurin-NFAT signaling pathway.
authors: Department of Cardiology, People's Hospital, Peking University, No. 11 South Avenue, Xi Zhi Men Xicheng District, Beijing 100044, China.
authors: Xiaoxia
authors: X
authors: Guo
authors: Chunyan
authors: C
authors: Zhou
authors: Ningling
authors: N
authors: Sun
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D053379:Chromogranin A / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction
chemical_list: D018680:Cholinergic Antagonists; D053379:Chromogranin A; D050778:NFATC Transcription Factors; D010446:Peptide Fragments; C109084:chromogranin A (344-364); D019703:Calcineurin; D002118:Calcium