Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-12-23
pubmed:abstractText
Mesoangioblasts are vessel-derived progenitor cells that can be induced to differentiate into different cell types of the mesoderm such as muscle and bone. Here we examined the role of transforming growth factor-beta (TGFbeta), a pleiotropic cytokine that plays a major role in development and specifically induces smooth muscle differentiation of mesoangioblasts, in the regulation of death and survival of these cells. TGFbeta exerts a marked anti-apoptotic action in mesoangioblasts with a mechanism involving regulation of sphingosine kinase 1 (SphK1), one of the isoforms responsible for S1P formation. Treatment with the cytokine efficaciously protected mesoangioblasts from apoptosis induced by serum starvation or staurosporine treatment assessed by various means such as activation of caspase-3, determination of cytoplasmic histone-associated-DNA-fragments and PE-AnnexinV staining. The protective action of TGFbeta from staurosporine-induced apoptosis was strongly reduced when the SphK activity was inhibited by drugs, when SphK1 but not SphK2 was downregulated by specific siRNA and when a SphK1 dominant negative mutant was overexpressed. Staurosporine treatment induced down-regulation of both SphK isoforms and TGFbeta rescued SphK1 but not SphK2 expression. Interestingly, TGFbeta strongly enhanced SphK activity during staurosporine-induced cell death. Both TGFbeta-induced SphK1 up-regulation and TGFbeta anti-apoptotic action were found to be dependent on p42/44 MAPK activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1873-3913
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
228-36
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
TGFbeta protects mesoangioblasts from apoptosis via sphingosine kinase-1 regulation.
pubmed:affiliation
Dipartimento di Scienze Biochimiche, Università di Firenze, 50134 Firenze, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't