Oxalate induces type II epithelial to mesenchymal transition (EMT) in inner medullary collecting duct cells (IMCD) in vitro and stimulate the expression of osteogenic and fibrotic markers in kidney medulla in vivo
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Marcia Convento1, Edson Pessoa1, Alef Aragão2, Nestor Schor1 and Fernanda Borges1,2
1Nephrology Division, Department of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil
2Interdisciplinary Postgraduate Program in Health Sciences, Universidade Cruzeiro do Sul, São Paulo, SP, Brazil
Marcia Convento, email: [email protected]
Keywords: epithelial to mesenchymal transition; osteogenic differentiation; oxalate; TGF-β1; renal medulla
Received: July 25, 2018 Accepted: January 12, 2019 Published: February 01, 2019
EMT occurs in response to a number of stresses conditions as mechanical stretch, cancer, hypoxia, oxidative stress (ROS), among others. EMT describes a phenotypical change induced in epithelial cells. It is characterized by increases in motility, extracellular matrix synthesis, proliferation, and invasiveness. The present study analyzed if oxalate ions (Ox) could induce EMT in IMCD cells. Ox (0.5 mM) and transforming growth factor beta (TGF-β1 20 ng/mL) exposition during 48 hours increased migration and invasiveness, increased mesenchymal marker expression (Vimentin, alpha-smooth muscle actin: α-SMA, TGF-β1) and decreased epithelial marker expression (E-cadherin). IMCD stimulated with Ox and TGF-β1 and then exposed to the osteogenic medium during 15 days significantly increased early osteogenic markers (RUNX-2 and Alkaline Phosphatase) expression. Hyperoxaluric mice fed with trans-4-hydroxy-L-proline (HPL) presented calcium oxalate crystal excretion, increased in TGF-β1 expression and collagen fibers deposition and increased early osteogenic markers (RUNX-2 and Alkaline Phosphatase) at 60 days. Our in vitro and in vivo results suggest that oxalate induces EMT in inner medulla collecting duct cells and it may be involved in fibrotic tissue development, osteogenic differentiation and calcium crystal production both implicated in nephrolithiasis.
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