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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 22
pubmed:dateCreated
2007-11-8
pubmed:abstractText
Mice deficient in the SDF1-chemokine-receptor CXCR4, exhibit severe defects of secondary limb myogenesis. To further elucidate the role of SDF1 in muscle development, we have now analyzed putative effects of this chemokine on proliferation, migration and myogenic differentiation of mouse C2C12 myogenic progenitor/myoblast cells. In addition, we have characterized the signaling pathways employed by SDF1-CXCR4 to control myogenesis. We found that SDF1 stimulates proliferation and induces migration of C2C12 cells with a potency similar to that of FGF2 and HGF, which both represent prototypical extracellular regulators of myogenesis. In addition, SDF1 inhibits myogenic differentiation in both C2C12 cells and primary myoblasts, as assessed by MyoD, myosin heavy chain and/or myogenin expression. Regarding signaling pathways, C2C12 cells responded to SDF1 with activation (phosphorylation) of Erk and PKCzeta, whereas even after prolonged SDF1 treatment for up to 120 minutes, levels of activated Akt, p38 and PKCalpha or PKCbeta remained unaffected. Preventing activation of the classic MAP kinase cascade with the Erk inhibitor UO126 abolished SDF1-induced proliferation and migration of C2C12 cells but not the inhibitory action of SDF1 on myogenic differentiation. Moreover, the effects of SDF1 on proliferation, migration and differentiation of C2C12 cells were all abrogated in the presence of myristoylated PKCzeta peptide pseudosubstrate and/or upon cellular depletion of PKCzeta by RNA interference. In conclusion, our findings unravel a previously unknown role of CXCR4-PKCzeta signaling in myogenesis. The potent inhibitory effects of SDF1 on myogenic differentiation point to a major function of CXCR4-PKCzeta signaling in the control of secondary muscle growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4050-9
pubmed:dateRevised
2009-4-7
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The chemokine SDF1 controls multiple steps of myogenesis through atypical PKCzeta.
pubmed:affiliation
Institute of Anatomy, Medical Faculty, University of Leipzig, Liebigstr. 13, 04103 Leipzig, Germany.
pubmed:publicationType
Journal Article