Osteopontin deletion attenuates cyst growth but exacerbates fibrosis in mice with cystic kidney disease.
Osteopontin
PKD
fibrosis
matricellular proteins
mineral metabolism
Journal
Physiological reports
ISSN: 2051-817X
Titre abrégé: Physiol Rep
Pays: United States
ID NLM: 101607800
Informations de publication
Date de publication:
Sep 2024
Sep 2024
Historique:
revised:
22
08
2024
received:
14
05
2024
accepted:
27
08
2024
medline:
6
9
2024
pubmed:
6
9
2024
entrez:
5
9
2024
Statut:
ppublish
Résumé
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.
Substances chimiques
Osteopontin
106441-73-0
Spp1 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70038Subventions
Organisme : HHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases (DEM)
ID : R01DK122212
Organisme : HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ID : R01DK129255
Organisme : HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ID : K01DK119375
Informations de copyright
© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
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