AI Article Synopsis
- Suv39h1 is a histone methyltransferase that plays a crucial role in gene silencing by trimethylating H3K9, and it has been observed that levels of Suv39h1 and H3K9me3 decrease in diabetic mouse vascular smooth muscle cells.
- High glucose (HG) conditions and the Suv39h1 inhibitor chaetocin lead to increased expression of fibronectin and p21(WAF1) while decreasing Suv39h1 levels and H3K9me3 marks at their gene promoters.
- Suv39h1 overexpression can counteract the effects of HG by reducing fibrosis-related gene expressions and promoting histone modifications, indicating that the PI3K pathway is involved
Article Abstract
Suppressor of variegation 3-9 homolog 1 (Suv39h1) is a histone methyltransferase that trimethylates lysine 9 of histone H3 (H3K9me3), which results in gene silencing. A previous study found that H3K9me3 and Suv39h1 were decreased in diabetic mouse vascular smooth muscle cells whereas Suv39h1 overexpression attenuated ischemic myocardial injury. Moreover, high glucose (HG) decreased H3K9me3 and Suv39h1 levels in some cells. Thus, we studied the roles of Suv39h1 in HG-induced effects in MES13 (mouse mesangial) cells. We found that HG, chaetocin (a Suv39h1 inhibitor) and Suv39h1 siRNA decreased Suv39h1 while increasing fibronectin and p21(WAF1) protein levels. HG increased mRNA while chaetocin increased transcription of fibronectin and p21(WAF1)genes. Both HG and chaetocin decreased histone H3K9me3 levels at the promoters of fibronectin and p21(WAF1) genes. Additionally, Suv39h1 overexpression attenuated HG-induced fibronectin and p21(WAF1) mRNA and protein expressions while attenuating HG-induced cell hypertrophy. Suv39h1 overexpression also attenuated HG-suppressed histone H3K9me3 levels at the promoters of fibronectin and p21(WAF1) genes. Moreover, LY294002 or the dominant-negative phosphoinositide 3-kinase (PI3K) mutant (Δp85) attenuated HG-decreased Suv39h1 and HG-induced fibronectin and p21(WAF1) protein expressions. We concluded that HG decreased Suv39h1 via the PI3K pathway in mesangial cells. Inhibition of Suv39h1 increased fibronectin and p21(WAF1) expressions. Moreover, Suv39h1 overexpression attenuated HG-induced fibronectin and p21(WAF1) expressions and cell hypertrophy while attenuating HG-suppressed histone H3K9me3 levels at the promoters of fibronectin and p21(WAF1) genes.
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| http://dx.doi.org/10.1016/j.biocel.2016.06.021 | DOI Listing |
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