Gestational low-protein intake enhances the whole kidney miR-192 and miR-200 family expression and epithelial-to-mesenchymal transition in adult male offspring

ABSTRACT Background Studies have been showed that maternal protein-restricted adult offspring, present pronounced reduction of nephron number associated with decreased fractional urinary sodium excretion and arterial hypertension. Also, recent advances in our understanding of the molecular pathways that govern the association of gestational nutritional restriction, intrauterine growth retardation inflammation with impaired nephrogenesis, nephron underdosing and kidney fibrosis point to the epithelial to mesenchymal transition (EMT) as the common. Method In the current study, the protein and sodium urinary excretion rates were evaluated and immunohistochemistry and western blot techniques were used to characterize the whole kidney structure changes in 16-wk old male LP offspring compared with age-matched controls. We also verify the expression of miRNAs, mRNAs and proteins markers of fibrosis and epithelial-to-mesenchymal transition in entire kidney prepared from LP offspring. Results In the current study, we may assume that arterial hypertension and long-term hyperfiltration process manifests, itself by proteinuria was accompanied by increased whole kidney mRNA expression of TGF-β1, ZEB1, type I collagen and, fibronectin in parallel to decreased expression of E-cadherin in 16-wk old LP offspring. Surprisingly, the renal tissue miR-129, miR-141, miR-200c and miR-429 were significantly upregulated in LP offspring compared to age-matched NP rats. Conclusion Considering that the overload in remaining nephrons, we may state that hypertension and proteinuria development following maternal protein restriction, may be a preponderant factor for the development of EMT and fibrous process and altered kidney ultrastructure in rat offspring. However, further studies are required to assess the contribution of miRNAs on renal injury progression in gestational protein-restricted model of fetal programming.