Abstract：
:Myogenic differentiation in adult muscle is normally suppressed and can be activated by myogenic cues in a subset of activated satellite cells. The switch mechanism that turns myogenesis on and off is not defined. In the present study, we demonstrate that tissue inhibitor of metalloproteinase 3 (TIMP3), the endogenous inhibitor of TNFalpha-converting enzyme (TACE), acts as an on-off switch for myogenic differentiation by regulating autocrine TNFalpha release. We observed that constitutively expressed TIMP3 is transiently downregulated in the satellite cells of regenerating mouse hindlimb muscles and differentiating C2C12 myoblasts. In C2C12 myoblasts, perturbing TIMP3 downregulation by overexpressing TIMP3 blocks TNFalpha release, p38 MAPK activation, myogenic gene expression and myotube formation. TNFalpha supplementation at a physiological concentration rescues myoblast differentiation. Similarly, in the regenerating soleus, overexpression of TIMP3 impairs release of TNFalpha and myogenic gene expression, and delays the formation of new fibers. In addition, downregulation of TIMP3 is mediated by the myogenesis-promoting microRNA miR-206. Thus, TIMP3 is a physiological regulator of myogenic differentiation.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Liu H,Chen SE,Jin B,Carson JA,Niu A,Durham W,Lai JY,Li YPdoi
10.1242/jcs.057620subject
Has Abstractpub_date
2010-09-01 00:00:00pages
2914-21issue
Pt 17eissn
0021-9533issn
1477-9137pii
jcs.057620journal_volume
123pub_type
杂志文章abstract：:Insect ovarian Sf9 cells extend processes with complex morphologies when infected with a recombinant baculovirus encoding the catalytic subunit of protein kinase A. Within the shafts of the processes are abundant microtubules, which, in contrast to those in Sf9 cells expressing the microtubule-associated protein tau, ...
journal_title：Journal of cell science
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
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pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
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pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
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