Eintrag weiter verarbeiten
Verfügbar über Online-Ressource

Histone Lysine Methylation in TGF-β1 Mediated p21 Gene Expression in Rat Mesangial Cells

Gespeichert in:

Bibliographische Detailangaben
Zeitschriftentitel: BioMed Research International
Personen und Körperschaften: Guo, Qiaoyan, Li, Xiaoxia, Han, Hongbo, Li, Chaoyuan, Liu, Shujun, Gao, Wenhui, Sun, Guangdong
In: BioMed Research International, 2016, 2016, S. 1-9
Format: E-Article
Sprache: Englisch
veröffentlicht:
Hindawi Limited
Schlagwörter:
General Immunology and Microbiology
General Biochemistry, Genetics and Molecular Biology
General Medicine
Details
Zusammenfassung: <jats:p>Transforming growth factor beta1- (TGF-<jats:italic>β</jats:italic>1-) induced p21-dependent mesangial cell (MC) hypertrophy plays a key role in the pathogenesis of chronic renal diseases including diabetic nephropathy (DN). Increasing evidence demonstrated the role of posttranscriptional modifications (PTMs) in the event; however, the precise regulatory mechanism of histone lysine methylation remains largely unknown. Here, we examined the roles of both histone H3 lysine 4 and lysine 9 methylations (H3K4me/H3K9me) in TGF-<jats:italic>β</jats:italic>1 induced p21 gene expression in rat mesangial cells (RMCs). Our results indicated that TGF-<jats:italic>β</jats:italic>1 upregulated the expression of p21 gene in RMCs, which was positively correlated with the increased chromatin marks associated with active genes (H3K4me1/H3K4me2/H3K4me3) and negatively correlated with the decreased levels of repressive marks (H3K9me2/H3K9me3) at p21 gene promoter. TGF-<jats:italic>β</jats:italic>1 also elevated the recruitment of the H3K4 methyltransferase (HMT) SET7/9 to the p21 gene promoter. SET7/9 gene silencing with small interfering RNAs (siRNAs) significantly abolished the TGF-<jats:italic>β</jats:italic>1 induced p21 gene expression. Taken together, these results reveal the key role of histone H3Kme in TGF-<jats:italic>β</jats:italic>1 mediated p21 gene expression in RMC, partly through HMT SET7/9 occupancy, suggesting H3Kme and SET7/9 may be potential renoprotective agents in managing chronic renal diseases.</jats:p>
Umfang: 1-9
ISSN: 2314-6133
2314-6141
DOI: 10.1155/2016/6927234