ArticleJournal of the American Society of Nephrology : JASN2016
Mammalian Target of Rapamycin Mediates Kidney Injury Molecule 1-Dependent Tubule Injury in a Surrogate Model.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Biomarkers Associated With Severe COVID-19 Among Populations With High Cardiometabolic Risk: A 2-Sample Mendelian Randomization Study.JAMA network open · 2023Pooled it
- From acute tubular injury to tubular repair and chronic kidney diseases - KIM-1 as a promising biomarker for predicting renal tubular pathology.Current research in physiology · 2025Review
- Emo@KP MBs Modulates the TGF-β1/Smad Signaling Pathway by in situ Micro-Nano Conversion to Reduce Renal Inflammation and Fibrosis Caused by Unilateral Ureteral Obstruction.International journal of nanomedicine · 2025Article
- Bi-functional KIT-PR1P peptides combine with VEGF to protect ischemic kidney in rats by targeting to Kim-1.Regenerative therapy · 2024Article
- Experimental models of acute kidney injury for translational research.Nature reviews. Nephrology · 2022Review
- Identifying Common Molecular Mechanisms in Experimental and Human Acute Kidney Injury.Seminars in nephrology · 2022Review
- Specific bFGF targeting of KIM-1 in ischemic kidneys protects against renal ischemia-reperfusion injury in rats.Regenerative biomaterials · 2022Article
- Novel zebrafish polycystic kidney disease models reveal functions of the Hippo pathway in renal cystogenesis.Disease models & mechanisms · 2021Article
- Innate Immune Response to Fasting and Refeeding in the Zebrafish Kidney.Biomolecules · 2021Article
- High-Fat Diet-Induced Renal Proximal Tubular Inflammatory Injury: Emerging Risk Factor of Chronic Kidney Disease.Frontiers in physiology · 2021Review
- The role of phosphatidylserine recognition receptors in multiple biological functions.Cellular & molecular biology letters · 2020Review
- Kidney injury molecule-1, a sensitive and specific marker for identifying acute proximal tubular injury, can be used to predict renal functional recovery in native renal biopsies.International urology and nephrology · 2019Article
- Inactivation ofAmerican journal of physiology. Renal physiology · 2019Article
- Comparison of anti-peritoneal fibrotic effects between an mTORC1-specific blocker and a PI3K/mTOR dual-blocker.Renal failure · 2019Article
- Kidney Injury Molecule-1 Is Upregulated in Renal Lipotoxicity and Mediates Palmitate-Induced Tubular Cell Injury and Inflammatory Response.International journal of molecular sciences · 2019Article
- The role of macrophages during acute kidney injury: destruction and repair.Pediatric nephrology (Berlin, Germany) · 2019Review
- Kidney injury molecule-1 identifies antemortem injury in postmortem adult and fetal kidney.American journal of physiology. Renal physiology · 2018Article
- Uromodulin deficiency alters tubular injury and interstitial inflammation but not fibrosis in experimental obstructive nephropathy.Physiological reports · 2018Article
- PGC1α in the kidney.American journal of physiology. Renal physiology · 2018Review
- Relationship of proximal tubular injury to chronic kidney disease as assessed by urinary kidney injury molecule-1 in five cohort studies.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2016Observational
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Kidney injury molecule 1 (KIM-1), an epithelial phagocytic receptor, is markedly upregulated in the proximal tubule in various forms of acute and chronic kidney injury in humans and many other species. Whereas acute expression of KIM-1 has adaptive anti-inflammatory effects, chronic expression may be maladaptive in mice. Here, we characterized the zebrafish Kim family, consisting of Kim-1, Kim-3, and Kim-4. Kim-1 was markedly upregulated in kidney after gentamicin-induced injury and had conserved phagocytic activity in zebrafish. Both constitutive and tamoxifen-induced expression of Kim-1 in zebrafish kidney tubules resulted in loss of the tubule brush border, reduced GFR, pericardial edema, and increased mortality. Kim-1-induced kidney injury was associated with reduction of growth of adult fish. Kim-1 expression led to activation of the mammalian target of rapamycin (mTOR) pathway, and inhibition of this pathway with rapamycin increased survival. mTOR pathway inhibition in KIM-1-overexpressing transgenic mice also significantly ameliorated serum creatinine level, proteinuria, tubular injury, and kidney inflammation. In conclusion, persistent Kim-1 expression results in chronic kidney damage in zebrafish through a mechanism involving mTOR. This observation predicted the role of the mTOR pathway and the therapeutic efficacy of mTOR-targeted agents in KIM-1-mediated kidney injury and fibrosis in mice, demonstrating the utility of the Kim-1 renal tubule zebrafish models.
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