Calcium oxalate crystals and oxalate induce an epithelial-to-mesenchymal transition in the proximal tubular epithelial cells: Contribution to oxalate kidney injury

• Autor(a) principal: Convento, Marcia Bastos [UNIFESP]
• Data de Publicação: 2017
• Outros Autores: Pessoa, Edson Andrade [UNIFESP], Cruz, Edgar [UNIFESP], da Gloria, Maria Aparecida [UNIFESP], Schor, Nestor [UNIFESP], Borges, Fernanda Teixeira [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/001300000n6vz
• DOI: 10.1038/srep45740
• Texto Completo: http://dx.doi.org/10.1038/srep45740; https://repositorio.unifesp.br/handle/11600/54723

TGF-beta 1 is the main mediator of epithelial-to-mesenchymal transition (EMT). Hyperoxaluria induces crystalluria, interstitial fibrosis, and progressive renal failure. This study analyzed whether hyperoxaluria is associated with TGF-beta 1 production and kidney fibrosis in mice and if oxalate or calcium oxalate (CaOx) could induce EMT in proximal tubule cells (HK2) and therefore contribute to the fibrotic process. Hyperoxaluria was induced by adding hydroxyproline and ethylene glycol to the mice's drinking water for up to 60 days. Renal function and oxalate and urinary crystals were evaluated. Kidney collagen production and TGF-beta 1 expression were assessed. EMT was analyzed in vitro according to TGF-beta 1 production, phenotypic characterization, invasion, cell migration, gene and protein expression of epithelial and mesenchymal markers. Hyperoxaluric mice showed a decrease in renal function and an increase in CaOx crystals and Ox urinary excretion. The deposition of collagen in the renal interstitium was observed. HK2 cells stimulated with Ox and CaOx exhibited a decreased expression of epithelial as well as increased expression mesenchymal markers