KLF transcription factors in metabolic kidney disease: from podocyte protection to tubulointerstitial fibrosis.

Authors

Yuntian Shi, Kexin Zhang, Jinyan Chen, Chengxia Kan, Fang Han, Xiaodong Sun, Zhentao Guo

Published in

International urology and nephrology. Sep 17, 2026. Epub Sep 17, 2026.

Abstract

Metabolic kidney disease comprises renal disorders driven or worsened by systemic metabolic abnormalities, including diabetic kidney disease, obesity-related kidney injury, hyperuricemia-associated nephropathy, and metabolic syndrome-associated chronic kidney disease. Despite different triggers, these disorders share podocyte injury, glomerular endothelial dysfunction, tubular lipotoxicity, mitochondrial impairment, oxidative stress, inflammation, and tubulointerstitial fibrosis, indicating a common program of metabolic stress-induced renal cell reprogramming. Krüppel-like factors (KLFs) are zinc-finger transcription factors that regulate cell differentiation, metabolic homeostasis, redox balance, inflammation, vascular integrity, epithelial function, and tissue remodeling. Emerging evidence suggests that KLF family members function as cell-specific and disease-stage-dependent regulators linking metabolic disturbance to kidney injury and repair. KLF15, KLF2, and KLF4 generally maintain podocyte integrity, endothelial quiescence, tubular metabolic adaptation, mitochondrial homeostasis, and anti-inflammatory responses, whereas KLF5, KLF6, and possibly KLF10 promote tubular activation, immune recruitment, transforming growth factor-β signaling, fibroblast activation, and extracellular matrix deposition during chronic injury. This review summarizes current evidence on KLFs in metabolic kidney disease, highlights process-specific mechanisms across renal compartments, and discusses therapeutic opportunities, delivery challenges, and the potential value of KLF-related signatures as biomarkers. By integrating protective and pathogenic KLF programs, it provides a framework for understanding transcriptional control in metabolically stressed kidneys and progressive renal decline.

PMID:
42753072
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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