Kruppel-like factor 4 improves obesity-related nephropathy through increasing mitochondrial biogenesis and activities.

Abstract

Obesity is positively linked to multiple metabolic complications including renal diseases. Several studies have demonstrated Kruppel-like factor 4 (KLF4) participated in renal dysfunction and structural disorders in acute kidney injuries, but whether it affected the process of chronic kidney diseases was unknown. Therefore, present study was to disclose the role of renal KLF4 in dietary-induced renal injuries and underlying mechanisms in obesity. Through utilizing high-fat diet-fed mice and human renal biopsies, we provided the physiological roles of KLF4 in protecting against obesity-related nephropathy. Decreased levels of renal KLF4 were positively correlated with dietary-induced renal dysfunction, including increased levels of creatinine and blood urea nitrogen. Overexpression of renal KLF4 suppressed inflammatory response in palmitic acid-treated mouse endothelial cells. Furthermore, overexpressed KLF4 also attenuated dietary-induced renal functional disorders, abnormal structural remodelling and inflammation. Mechanistically, KLF4 maintained renal mitochondrial biogenesis and activities to combat obesity-induced mitochondrial dysfunction. In clinical renal biopsies and plasma, the renal Klf4 level was negatively associated with circulating levels of creatinine but positively associated with renal creatinine clearance. In conclusions, the present findings firstly supported that renal KLF4 played an important role in combating obesity-related nephropathy, and KLF4/mitochondrial function partially determined the energy homeostasis in chronic kidney diseases.

• Authors: Lingwei Jin, Hanyang Ye, Min Pan, Yan Chen, Bairu Ye, Yu Zheng, Wenwen Huang, Shufang Pan, Zhen Shi, Jing Zhang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 2 Pg. 1200-1207 (01 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 31800161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• KLF4 protein, human
• Klf4 protein, mouse
• Kruppel-Like Factor 4
• Kruppel-Like Transcription Factors

Topics

• Acute Kidney Injury (etiology, metabolism, pathology, prevention & control)
• Animals
• Diet, High-Fat (adverse effects)
• Humans
• Inflammation (etiology, metabolism, pathology, prevention & control)
• Kruppel-Like Factor 4
• Kruppel-Like Transcription Factors (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Obesity (complications)
• Organelle Biogenesis