ArticleAmerican journal of physiology. Renal physiology2014
ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 41 citations in OpenAlex.
- ADAM9 Promotes Glycolysis in Th17 Cells and Autoimmunity Through Activation of IGF-1 Signaling.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- ANKHD1 promotes pathogenic proliferation in Autosomal Dominant Polycystic Kidney Disease via the Cyclin D1/CDK4 pathway.Journal of translational medicine · 2025Article
- mInternational journal of oncology · 2024Article
- Knockdown of DEC2 expression inhibits the proliferation of mesangial cells through suppressed glycolysis and p38 MAPK/Erk pathway in lupus nephritis.Molecular medicine (Cambridge, Mass.) · 2023Article
- ADAM10 and ADAM17, Major Regulators of Chronic Kidney Disease Induced Atherosclerosis?International journal of molecular sciences · 2023Review
- Article
- Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing.Pathogens (Basel, Switzerland) · 2022Review
- ADAMs family in kidney physiology and pathology.EBioMedicine · 2021Review
- IFT88 deficiency in proximal tubular cells exaggerates cisplatin-induced injury by suppressing autophagy.American journal of physiology. Renal physiology · 2021Article
- Key metalloproteinase-mediated pathways in the kidney.Nature reviews. Nephrology · 2021Review
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases.Frontiers in physiology · 2021Review
- Glucose Metabolism in Acute Kidney Injury and Kidney Repair.Frontiers in medicine · 2021Review
- Activity-dependent neuronal Klotho enhances astrocytic aerobic glycolysis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Review
- Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease.Nutrients · 2018Article
- ADAM-17 is expressed on rheumatoid arthritis fibroblast-like synoviocytes and regulates proinflammatory mediator expression and monocyte adhesion.Arthritis research & therapy · 2018Article
- Cilia protein IFT88 regulates extracellular protease activity by optimizing LRP-1-mediated endocytosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Short hairpin RNA-mediated gene silencing of ADAM17 inhibits the growth of breast cancer MCF‑7 cells in vitro and in vivo and its mechanism of action.Oncology reports · 2018Article
- Lkb1 deficiency confers glutamine dependency in polycystic kidney disease.Nature communications · 2018Article
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8 authors at 3 institutions in 2 countries.
Funding
Abstract
Polycystic kidney disease (PKD) is a common genetic disorder leading to cyst formation in the kidneys and other organs that ultimately results in kidney failure and death. Currently, there is no therapy for slowing down or stopping the progression of PKD. In this study, we identified the disintegrin metalloenzyme 17 (ADAM17) as a key regulator of cell proliferation in kidney tissues of conditional knockout Ift88(-/-) mice and collecting duct epithelial cells from Ift88°(rpk) mice, animal models of autosomal recessive polycystic kidney disease (ARPKD). Using Western blotting, an enzyme activity assay, and a growth factor-shedding assay in the presence or absence of the specific ADAM17 inhibitor TMI-005, we show that increased expression and activation of ADAM17 in the cystic kidney and in collecting duct epithelial cells originating from the Ift88°(rpk) mice (designated as PKD cells) lead to constitutive shedding of several growth factors, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin, and transforming growth factor-α (TGF-α). Increased growth factor shedding induces activation of the EGFR/MAPK/ERK pathway and maintains higher cell proliferation rate in PKD cells compared with control cells. PKD cells also displayed increased lactate formation and extracellular acidification indicative of aerobic glycolysis (Warburg effect), which was blocked by ADAM17 inhibition. We propose that ADAM17 is a key promoter of cellular proliferation in PKD cells by activating the EGFR/ERK axis and a proproliferative glycolytic phenotype.
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