title: Involvement of renal corpuscle microRNA expression on epithelial-to-mesenchymal transition in maternal low protein diet in adult programmed rats.
abstract: 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-β1 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 1α1/2 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-β1 action inducing ZEB 2 expression that may subsequently cause glomeruli epithelial-to-mesenchymal transition.
authors: Fetal Programming Laboratory, Morphology Department, São Paulo State University, Botucatu, São Paulo, Brazil.
authors: Letícia de Barros
authors: Lde B
authors: Sene
authors: Flávia Fernandes
authors: FF
authors: Mesquita
authors: Leonardo Nazário
authors: LN
authors: de Moraes
authors: Daniela Carvalho
authors: DC
authors: Santos
authors: Robson
authors: R
authors: Carvalho
authors: José Antônio Rocha
authors: JA
authors: Gontijo
authors: Patrícia Aline
authors: PA
authors: Boer
mesh_terms: D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000235:genetics*; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D003893:Desmin; D005353:Fibronectins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; C407223:NPHS2 protein; D053773:Transforming Growth Factor beta1; C113267:nephrin; D003094:Collagen
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