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Decline of p300 contributes to cell senescence and growth inhibition of hUC-MSCs through p53/p21 signaling pathway.

Abstract：

:Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in vitro expansion for long term may undergo epigenetic and genetic alterations that subsequently induce cellular senescence and associated growth inhibition. Increasing evidence implicated that aberrant histone acetylation modulates gene expression responsible for MSCs aging. Whether the dysregulation of p300 and its KAT activity is involved in the aging process of MSCs was still unexplored. In this study, we found a significant decrease of p300 but elevated p53/p21 levels in senescent hUC-MSCs at late-passage. Then we used two different approaches: (i) downregulation of p300 by siRNA and (ii) inhibition of the acetyltransferase(KAT) activity by C646 to determine the role of p300 in regulating MSCs senescence. We showed that inhibition of p300 induce premature senescence and decrease proliferation potential in hUC-MSCs. Moreover, upregulations of p53 and p21 expressions were confirmed in p300 knockdown and C646-treated hUC-MSCs. Taken together, these results suggest that p300 plays an important role in aging process of MSCs associated with activation of p53/p21 signaling pathway.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Li Y,Zhong H,Wu M,Tan B,Zhao L,Yi Q,Xu X,Pan H,Bi Y,Yang K

doi

10.1016/j.bbrc.2019.05.061

subject

Has Abstract

pub_date

2019-07-12 00:00:00

pages

24-30

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)30931-3

journal_volume

515

pub_type

杂志文章

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