Osteopontin deletion attenuates cyst growth but exacerbates fibrosis in mice with cystic kidney disease.

Autor: Jansson KP; The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA.; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Kuluva J; The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA., Zhang S; The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA., Swanson T; The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA., Zhang Y; The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA., Zimmerman KA; Division of Nephrology, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA., Fields TA; The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA.; Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Wallace DP; The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA.; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Rowe PS; The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA.; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA., Stubbs JR; The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas, USA.; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
Jazyk: angličtina
Zdroj: Physiological reports [Physiol Rep] 2024 Sep; Vol. 12 (17), pp. e70038.
DOI: 10.14814/phy2.70038
Abstrakt: Osteopontin (OPN) is a multi-functional glycoprotein that coordinates the innate immune response, prevents nanocrystal formation in renal tubule fluid, and is a biomarker for kidney injury. OPN expression is markedly increased in cystic epithelial cells of polycystic kidney disease (PKD) kidneys; however, its role in PKD progression remains unclear. We investigated the in vitro effects of recombinant OPN on the proliferation of tubular epithelial cells from PKD and normal human kidneys and in vivo effects of OPN deletion on kidney cyst formation, fibrosis, and mineral metabolism in pcy/pcy mice, a non-orthologous model of autosomal-dominant PKD. In vitro studies revealed that OPN enhanced the proliferation of PKD cells but had no effect on normal kidney cells. Deletion of OPN in pcy/pcy mice significantly reduced kidney cyst burden; however, this was accompanied by increased fibrosis and no change in kidney function. The loss of OPN had no effect on kidney macrophage numbers, cyst epithelial cell proliferation, or apoptosis. Furthermore, there was no difference in kidney mineral deposition or mineral metabolism parameters between pcy/pcy mice with and without OPN expression. Global deletion of OPN reduced kidney cyst burden, while paradoxically exacerbating kidney fibrosis in mice with cystic kidney disease.
(© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
Databáze: MEDLINE
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