Involvement of Renal Corpuscle microRNA Expression on Epithelial-to-Mesenchymal Transition in Maternal Low Protein Diet in Adult Programmed Rats

Sene, Leticia de Barros [UNESP]; Mesquita, Flavia Fernandes; Moraes, Leonardo Nazario de [UNESP]; Santos, Daniela Carvalho [UNESP]; Carvalho, Robson [UNESP]; Rocha Gontijo, Jose Antonio; Boer, Patricia Aline [UNESP]

Involvement of Renal Corpuscle microRNA Expression on Epithelial-to-Mesenchymal Transition in Maternal Low Protein Diet in Adult Programmed Rats

Arquivos

WOS000323425700037.pdf (2.34 MB)

Data

2013-08-19

Autores

Sene, Leticia de Barros

Mesquita, Flavia Fernandes

Moraes, Leonardo Nazario de

Santos, Daniela Carvalho

Carvalho, Robson

Rocha Gontijo, Jose Antonio

Boer, Patricia Aline

Editor

Public Library Science

Tipo

Artigo

Direito de acesso

Acesso aberto

Resumo

Prior study shows that maternal protein-restricted (LP) 16-wk-old offspring have pronounced reduction of nephron number and arterial hypertension associated with unchanged glomerular filtration rate, besides enhanced glomerular area, which may be related to glomerular hyperfiltration/overflow and which accounts for the glomerular filtration barrier breakdown and early glomerulosclerosis. In the current study, LP rats showed heavy proteinuria associated with podocyte simplification and foot process effacement. TGF-beta 1 glomerular expression was significantly enhanced in LP. Isolated LP glomeruli show a reduced level of miR-200a, miR-141, miR-429 and ZEB2 mRNA and upregulated collagen 1 alpha 1/2 mRNA expression. By western blot analyzes of whole kidney tissue, we found significant reduction of both podocin and nephrin and enhanced expression of mesenchymal protein markers such as desmin, collagen type I and fibronectin. From our present knowledge, these are the first data showing renal miRNA modulation in the protein restriction model of fetal programming. The fetal-programmed adult offspring showed pronounced structural glomerular disorders with an accentuated and advanced stage of fibrosis, which led us to state that the glomerular miR-200 family would be downregulated by TGF-beta 1 action inducing ZEB 2 expression that may subsequently cause glomeruli epithelial-to-mesenchymal transition.