Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(7), P. 1881 - 1881

Published: March 25, 2024

Chronic kidney disease (CKD) is a slowly progressive condition characterized by decreased function, tubular injury, oxidative stress, and inflammation. CKD leading global health burden that asymptomatic in early stages but can ultimately cause failure. Its etiology complex involves dysregulated signaling pathways lead to fibrosis. Transforming growth factor (TGF)-β central mediator promoting transdifferentiation of polarized renal epithelial cells into mesenchymal cells, resulting irreversible injury. While current therapies are limited, the search for more effective diagnostic treatment modalities intensive. Although biopsy with histology most accurate method diagnosis staging, imaging techniques such as diffusion-weighted magnetic resonance shear wave elastography ultrasound less invasive ways stage Current renin-angiotensin blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitors aim delay progression. Newer antifibrotic agents suppress downstream inflammatory mediators involved fibrotic process clinical trials, potential therapeutic targets interfere TGF-β being explored. Small interfering RNAs stem cell-based therapeutics also evaluated. Further research studies necessary order avoid dialysis transplantation.

Language: Английский

Ankrd1 as a potential biomarker for the transition from acute kidney injury to chronic kidney disease

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 7, 2025

Ischemia-reperfusion injury (IRI) is one of the leading causes acute kidney (AKI), predisposing patients to chronic disease (CKD) due maladaptive renal repair. Nevertheless, molecular mechanisms and biomarkers that cause repair remain unclear. In this study, we used single-nucleus RNA sequencing data from GEO database (GSE139107) identify markers during transition AKI CKD caused by IRI. Analysis intercellular crosstalk, trajectory machine learning algorithms revealed hub cell clusters genes. Proximal tubule (PT) cells, especially a new cluster (New PT2), significantly interacted with fibroblasts transition. The expression levels genes were validated using bulk RNA-seq (GSE98622) further confirmed through RT-qPCR immunohistochemical analysis in ischemia-reperfusion (uIRI) mice. Ankrd1, gene New PT2, showed sustained upregulation proximal AKI. Compared sham-operated group, Ankrd1 mice increased at 0.5 days post-reperfusion, peaked day 1, remained elevated up 60 days. This study indicated was positively associated progression may potentially serve as valuable biomarker for transitional process.

Language: Английский

Network pharmacology combined with transcriptomics reveals that formononetin, a biologically component of Astragalus membranaceus (Fisch.) Bunge, inhibits the PI3K/Akt signaling pathway to improve chronic renal failure

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 338, P. 119041 - 119041

Published: Nov. 6, 2024

Language: Английский