This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

proofread

Study reveals the role of ERRγ in the regulation of FGF23 gene expression following acute liver injury

New study reveals the role of ERRγ in the regulation of FGF23 gene expression following acute liver injury
CCl4-induced acute liver injury increases FGF23 gene expression and secretion in mouse liver through ERRγ. (A, B) Quantitative PCR analysis of total RNA obtained from the livers of mice injected with CCl4 (1 mL/kg body weight of 10% CCl4 dissolved in corn oil) for 6 h (n = 5 per group). (C–F) WT and ERRγ-LKO mice were injected with CCl4 for 6 h (n = 5 per groups). (C) Quantitative PCR analysis of total RNA isolated from livers. (D) Representative images of FGF23 immunohistochemical analysis in liver sections. (E) Representative in vivo images of hepatic FGF23 promoter WT-luciferase (Ad-FGF23-luc) activity in WT and ERRγ-LKO mice injected with or without CCl4 (n = 4 for WT-Con and ERRγ-LKO Con; n = 6 for WT-CCl4 and ERRγ-LKO CCl4 group). (F) Plasma FGF23 levels measured by ELISA. (G–I) WT mice were injected with CCl4 in the presence or the absence of GSK5182 and sacrificed after 6 h (n = 5 per group). (G) Quantitative PCR analysis of total RNA isolated from liver. (H) Representative images of FGF23 immunohistochemical analysis in liver sections. (I) Plasma FGF23 levels measured by ELISA. (J) Schematic diagram of ERRγ-mediated hepatic FGF23 gene expression and secretion in CCl4-induced acute liver injury. Data indicate mean ± SEM values. Data in (A) and (B) were analyzed by two-tailed Student's t test. Data in C, E, F, G and I were analyzed by ordinary one-way ANOVA with Tukey's multiple comparisons test. Significance levels denoted as ∗P < 0.05; ∗∗∗P < 0.001; n.s., not significant. Credit: Genes & Diseases (2022). DOI: 10.1016/j.gendis.2022.06.003

In a study published in the journal of Genes & Diseases, a team of researchers from Chonnam National University and the Korea Research Institute of Bioscience and Biotechnology unveiled important insights into liver injury and its underlying molecular mechanisms.

They discovered that CCl4 injections triggered a surge in pro-inflammatory cytokine interleukin-6 (IL6) mRNA in liver tissues, leading to an elevated presence of markers, (ALT) and aspartate aminotransferase (AST), in the blood plasma. Interestingly, kidney tissues were unaffected, with kidney injury markers, blood urea nitrogen (BUN) and creatinine, remaining stable.

The study builds on earlier findings, which showed that the estrogen-related receptor gamma (ERRγ) transcriptionally regulates the fibroblast growth factor 23 (FGF23) gene expression in the liver in response to folic acid-induced (FA-AKI). The current research reveals ERRγ's crucial role as an upstream regulator of hepatic FGF23 gene expression following CCl4-induced acute liver injury.

This was demonstrated by the noticeable reduction in hepatic ERRγ and FGF23 mRNA expression in ERRγ-LKO mice compared to CCl4-injected control mice.

The team used an innovative approach involving a mouse FGF23 promoter luciferase construct fused with adenovirus (Ad-FGF23-luc) to discern the molecular mechanism governing ERRγ-regulated FGF23 in response to CCl4-induced acute liver injury. In vivo imaging showed enhanced hepatic FGF23 promoter activity in CCl4-injected mice, underscoring the ERRγ's direct binding with the FGF23 promoter.

The use of a pharmacological ERRγ inhibitor, GSK5182, further supported these findings by significantly reducing CCl4-induced hepatic ERRγ and FGF23 mRNA expression.

The results underscore ERRγ's central role in the regulation of hepatic FGF23 production during CCl4-induced acute liver injury, suggesting that inhibiting ERRγ signaling could be a potential strategy for reducing abnormal circulatory FGF23 levels in acute liver injuries. These findings have for our understanding and potential treatment of liver and kidney injuries.

In conclusion, this research provides vital insights into the molecular underpinnings of acute liver injury and its connection to . It also lays the groundwork for future studies to potentially develop new therapeutic strategies targeting ERRγ to prevent or treat liver and kidney injuries.

More information: Yoon Seok Jung et al, Acute liver injury induces expression of FGF23 in hepatocytes via orphan nuclear receptor ERRγ signaling, Genes & Diseases (2022). DOI: 10.1016/j.gendis.2022.06.003

Provided by TranSpread
Citation: Study reveals the role of ERRγ in the regulation of FGF23 gene expression following acute liver injury (2023, September 14) retrieved 16 June 2024 from https://medicalxpress.com/news/2023-09-reveals-role-err-fgf23-gene.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Explore further

Understanding how hormones influence anemia

1 shares

Feedback to editors