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Cellular signalling

Cellular signalling

IF: 4.4
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ESRRA modulation by empagliflozin mitigates diabetic tubular injury via mitochondrial restoration

Published:24 July 2024 DOI: 10.1016/j.cellsig.2024.111308 PMID: 39059756
Keju Yang , Wei Liang , Hongtu Hu , Zongwei Zhang , Yiqun Hao , Zhixia Song , Lin Yang , Jijia Hu , Zhaowei Chen , Guohua Ding

Abstract

Background

The protection of the diabetic kidney by Empagliflozin (EMPA) is attributed to its interaction with the sodium glucose cotransporter 2 located on proximal tubular epithelial cells (PTECs). Estrogen-related receptor α (ESRRA), known for its high expression in PTECs and association with mitochondrial biogenesis, plays a crucial role in this process. This study aimed to explore the impact of ESRRA on mitochondrial mass in diabetic tubular injury and elucidate the mechanism underlying the protective effects of EMPA.

Methods

Mitochondrial changes in PTECs of 16-week-old diabetic mice were assessed using transmission electron microscopy (TEM) and RNA-sequences. In vivo, EMPA administration was carried out in db/db mice for 8?weeks, while in vitro experiments involved modifying ESRRA expression in HK2 cells using pcDNA-ESRRA or EMPA.

Results

Evaluation through TEM revealed reduced mitochondrial mass and swollen mitochondria in PTECs, whereas no significant changes were observed under light microscopy. Analysis of RNA-sequences identified 110 downregulated genes, including Esrra, associated with mitochondrial function. Notably, ESRRA overexpression rescued the loss of mitochondrial mass induced by high glucose (HG) in HK2 cells. EMPA treatment ameliorated the ultrastructural alterations and mitigated the downregulation of ESRRA both in db/db mice and HG-treated HK2 cells.

Conclusion

The diminished expression of ESRRA is implicated in the decline of mitochondrial mass in PTECs during the early stages of diabetes, highlighting it as a key target of EMPA for preventing the progression of diabetic kidney injury.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Empagliflozin 864070-44-0 C23H27ClO7 764 suppliers $5.00-$1950.00
Empagliflozin 864070-44-0 C23H27ClO7 764 suppliers $5.00-$1950.00
Empagliflozin 864070-44-0 C23H27ClO7 764 suppliers $5.00-$1950.00
Empagliflozin 864070-44-0 C23H27ClO7 764 suppliers $5.00-$1950.00
Empagliflozin 864070-44-0 C23H27ClO7 - Inquiry
Empagliflozin 864070-44-0 C23H27ClO7 - Inquiry
Empagliflozin 864070-44-0 - Inquiry
Empagliflozin 864070-44-0 - Inquiry

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