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

Autor(es)

Sene, Leticia de Barros ^[1] ; Mesquita, Flavia Fernandes ^[2] ; de Moraes, Leonardo Nazario ^[3] ; Santos, Daniela Carvalho ^[4] ; Carvalho, Robson ^[3] ; Rocha Gontijo, Jose Antonio ^[2] ; Boer, Patricia Aline ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Fetal Programming Lab, Dept Morphol, Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Renal Funct Lab, Dept Internal Med, Sao Paulo - Brazil

^[3] Sao Paulo State Univ, Striated Muscle Lab, Dept Morphol, Sao Paulo - Brazil

^[4] Sao Paulo State Univ, Dept Morphol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 8 AUG 19 2013.
• Citações Web of Science: 13

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. (AU)

• Processo FAPESP: 09/54141-9 - Aquisição de Microscópio Confocal a Laser Leica TCS SP5 e Microscópio Eletrônico de Transmissao TECNAI Spirit
• Beneficiário: Silvia Rodrigues Machado
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 10/52696-0 - Estudo dos mecanismos envolvidos no desenvolvimento renal e na expressão hipocampo-hipotalamo-hipofisaria de receptores esteróides e dopaminérgicos em prole de ratas submetidas a restrição protéica gestacional
• Beneficiário: Jose Antonio Rocha Gontijo
• Modalidade de apoio: Auxílio à Pesquisa - Regular