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The following is a summary of “ER-α36 prevents high glucose-induced cellular senescence and apoptosis in renal tubular cell,” published in the June 2025 issue of Frontiers in Endocrinology by Yu et al. 

Researchers conducted a retrospective study to analyze the effects of the estrogen-estrogen receptor (ER) system on renal tubular injury in diabetic kidney disease (DKD).  

They exposed human renal tubular (HK-2) cells to high glucose (HG) to simulate diabetic conditions. Apoptosis was measured using flow cytometry, and senescence was evaluated by β-Gal staining. Western blotting assessed ER-α36 expression, PI3K/AKT pathway activity, apoptosis regulators (Bcl-2, Bax, cleaved caspase-3/7), and senescence markers (P53, P21, P27, P16). The influence of ER-α36 on EZH2 and PTEN was investigated, while chromatin immunoprecipitation (ChIP) analyzed H3K27me3 modifications at the PTEN promoter.  

The results showed that HG treatment increased apoptosis and senescence in HK-2 cells, accompanied by suppression of PI3K/AKT signaling. These changes correlated with decreased EZH2 expression and reduced H3K27me3 at the PTEN promoter, causing PTEN upregulation. Overexpression of ER-α36 partially restored PI3K/AKT signaling, mitigated cellular damage and reversed epigenetic modifications at the PTEN site induced by HG.  

Investigators concluded that ER-α36 protected renal tubular cells from HG–induced injury by regulating PTEN epigenetically via EZH2 and activating the PI3K/AKT pathway, highlighting its potential as a therapeutic target for diabetic kidney disease in Nephrology. 

Source: frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1426854/full