The regulation of Schwann cell (SC) proliferation and morphology is critical to nerve homeostasis. We have previously reported that endothelins (ETs) regulate the activity of different effectors in SC including adenylyl cyclase, phospholipases C and A2 and mitogen-activated protein kinases (MAPKs). These effects imply a possible participation of ETs in the regulation of SC phenotype. We have now investigated the effects of endothelins on the proliferation and morphology of SC, and compared them with the responses to platelet-derived growth factor (PDGF), a known mitogen in these cells. Both @entity2232 ( @entity2232 ) and PDGF increased the incorporation of @entity665 and the proportion of SC in S and G2/M, with a concomitant decrease in the G0/G1 stage cells. Treatment with @entity2232 produced rapid changes in the morphology of the SC, characterized by the appearance of cell spreading with shorter processes. The response to @entity2232 was considered to represent a proliferative phenotype, in contrast to the effects of @entity1928 , which decreased @entity665 incorporation in immortalized SC (iSC) and lead to a differentiated morphology with longer extensions. While both @entity2232 and PDGF displayed a proliferative effect on SC, treatment with PDGF did not affect the morphology of these cells to a significant extent. A role for @entity1435 MAPK and @entity141 -independent @entity3900 in the changes in morphology and proliferation of iSC driven by @entity2232 was suggested by the effects of selective inhibitors of these pathways [ @entity4285 and HELSS, respectively]. The unique pattern of signaling pathways recruited by @entity2232 and its combined effects on regulation of phenotype and proliferation of SC suggest an important role for this peptide during @entity528 /regeneration.

Proliferative and morphological effects of endothelins in Schwann cells: roles of @entity1435 mitogen-activated protein kinase and XXXX -independent @entity3900 .

@entity2232 :: ('1906', 'Gene') :: ['endothelin-1', 'ET-1'] @entity665 :: ('CHEBI:53526', 'Chemical') :: ['[3H]thymidine'] @entity3900 :: ('151056', 'Gene') :: ['phospholipase A2'] @entity4285 :: ('MESH:C090942', 'Chemical') :: ['SB202190'] @entity1435 :: ('1432', 'Gene') :: ['p38'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity528 :: ('MESH:D009410', 'Disease') :: ['nerve degeneration'] @entity1928 :: ('MESH:D005576', 'Chemical') :: ['forskolin']
@entity141 :: (CHEBI:29108,Chemical) :: ['Ca(2+)']
