{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T08:35:47Z","timestamp":1780734947223,"version":"3.54.1"},"reference-count":38,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"abstract":"<jats:p>Introduction: Albuminuria is an independent risk factor for renal interstitial fibrosis and induces G2\/M phase arrest in proximal tubular epithelial cells. Although protein overload disrupts fatty acid metabolism, the mechanistic link to cell cycle arrest remains unclear. This study investigates the role of NIMA-related kinase 10 (NEK10), a serine\/threonine kinase implicated in cell cycle regulation, in mediating albumin-induced lipid dysregulation and G2\/M arrest, which exacerbate tubulointerstitial fibrosis. Methods: Human renal tubular cells (HK-2) were exposed to 10 mg\/mL bovine serum albumin (BSA) for 24\u201348 h. In vivo, NEK10 was knocked down using recombinant adenovirus (rAAV-shNEK10) in unilateral ureteral obstruction (UUO) mice treated with BSA. Clinically, NEK10 expression was assessed via immunohistochemistry in kidney biopsies from chronic kidney disease (CKD) patients with varying urinary protein levels. Results: BSA-exposed HK-2 cells showed lipid droplet accumulation, reduced ATP levels, impaired fatty acid oxidation, and increased G2\/M phase arrest. These effects coincided with upregulated NEK10 expression and ERK1\/2 phosphorylation. NEK10 knockdown in UUO mice attenuated BSA-induced renal fibrosis, lipid accumulation, and tubular injury. In CKD patients, elevated NEK10 expression correlated with higher urinary protein levels (&gt;3.5 g\/24 h) and interstitial fibrosis. Conclusion: Our findings identify NEK10 as a critical regulator of albumin-induced metabolic dysfunction and cell cycle arrest, suggesting therapeutic targeting of NEK10 may mitigate fibrosis in proteinuric kidney diseases.<\/jats:p>","DOI":"10.1159\/000547768","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T16:00:39Z","timestamp":1757606439000},"page":"1-19","source":"Crossref","is-referenced-by-count":1,"title":["NEK10 Drives Lipid Disturbances That Induce G2\/M Phase Arrest in Renal Tubular Cells under Albumin 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