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

Oncotarget
Marcia Bastos ConventoFernanda Teixeira Borges

Abstract

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 fibr...Continue Reading

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Citations

Jun 2, 2020·Frontiers in Oncology·Deborah P Lavin, Vijay K Tiwari
Jan 31, 2021·Nature Reviews. Nephrology·Saeed R KhanPaul R Dominguez-Gutierrez
Nov 27, 2021·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Victor Hugo CanelaJames C Williams

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Methods Mentioned

BETA
gastric bypass
PCR
fluorescence microscopy
electrophoresis
urine collection

Software Mentioned

ImageJ

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