Epigenetic restoration of endogenous Klotho expression alleviates acute kidney injury-diabetes comorbidity.

Abstract

AIMS:

The present study aimed at exploring the mechanisms behind Klotho regulation in hyperglycemia augmented AKI. In addition, epigenetic ways to restore the Klotho expression in AKI-diabetes comorbidity have been evaluated.

MAIN METHODS:

Bilateral ischemia-reperfusion injury (IRI) and chemical hypoxia-reperfusion injury (HRI) were developed in diabetic rats and, NRK52E cells under high glucose conditions respectively, to mimic the AKI condition. Plasma, urine, tubular lysate of the kidney and NRK52E cell lysate were used for biochemical, ELISA, histology, immunoblotting, RT-PCR and RNA interference studies.

KEY FINDINGS:

Hyperglycemia significantly aggravated IRI/HRI induced AKI as evidenced by biochemical and histological results. We also observed a significant increase in expressions of kidney specific histone deacetylases (HDACs), apoptotic and inflammatory proteins, and decrease in levels of endogenous Klotho, H3K9Ac and H3K27Ac proteins in hyperglycemic IRI/HRI groups.

SIGNIFICANCE:

Diabetes comorbidity exaggerates AKI, where endogenous Klotho loss could be a potential connecting link. However, kidney-specific HDACs inhibition showed reno-protection via restoring the endogenous Klotho loss and thus prevention of inflammation and apoptosis, which could prove to be a potential therapeutic strategy against diabetes-AKI comorbidity.

• Authors: Ajinath Kale, Himanshu Sankrityayan, Anil Bhanudas Gaikwad
• Journal: Life sciences (Life Sci) Vol. 288 Pg. 120194 (Jan 01 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 34864061 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Histone Deacetylase Inhibitors
• Klotho Proteins

Topics

• Acute Kidney Injury (etiology, metabolism, pathology, prevention & control)
• Animals
• Diabetes Mellitus, Experimental (complications)
• Diabetic Nephropathies (etiology, metabolism, pathology, prevention & control)
• Gene Expression Regulation (drug effects)
• Histone Deacetylase Inhibitors (pharmacology)
• Klotho Proteins (genetics, metabolism)
• Male
• Rats
• Rats, Wistar