Cyproheptadine, a SET7/9 inhibitor, reduces hyperglycaemia-induced ER stress alleviating inflammation and fibrosis in renal tubular epithelial cells

Abstract

Context

Persistent hyperglycaemia increases SET7/9 expression and endoplasmic reticulum (ER) stress which causes inflammation, apoptosis, and fibrosis in renal tubular epithelial cells leading to diabetic kidney disease (DKD).

Objective

Current study explores the renoprotective potential of a novel SET7/9 inhibitor, Cyproheptadine, and the underlying molecular mechanisms in hyperglycaemia-induced renal tubular epithelial cell injury.

Methods

Change in expression of SET7/9, histone H3 lysine (K4) monomethylation (H3K4Me1), inflammatory, fibrotic, and ER stress proteins were evaluated in-vivo and in-vitro. NRK-52E cells were used to study the preventive effect of Cyproheptadine against hyperglycaemia-induced ER stress and subsequent inflammation and fibrosis.

Results

SET7/9 and H3K4Me1 expression significantly increased with ER stress, inflammation, apoptosis, and fibrosis, in-vivo and in-vitro under hyperglycaemia. However, the cells treated with Cyproheptadine showed significant suppression of H3K4Me1 and reduction in ER stress, inflammation, apoptosis, and fibrosis.

Conclusion

Cyproheptadine prevented hyperglycaemia-induced renal fibrosis and inflammation by reducing H3K4Me1 expression and ER stress.

Keywords:

• Cyproheptadine
• SET7/9
• ER stress
• histone H3 lysine K4 mono-methylation
• diabetic kidney disease

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors agree to provide the current study's data on reasonable request.

Additional information

Funding

Anil Bhanudas Gaikwad sincerely acknowledges the financial support provided by Birla Institute of Technology and Science-Pilani, Pilani for carrying out this work.