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.

Renal sodium handling and blood pressure changes in gestational protein-restricted offspring: Role of renal nerves and ganglia neurokinin expression

“…The current study sustains a pathophysiological association between renal nerve activity, decreased renal sodium excretion, and enhanced blood pressure in maternal protein-deprived offspring model. The present data also confirmed that there was a significant reduction in the birthweight of LP male offspring compared with NP offspring [3–7]. This effect has been linked with a significant enhancement in arterial blood pressure beyond 7 weeks of age in LP rats relative to age-matched NP counterparts.…”

Fetal Kidney Programming by Maternal Smoking Exposure: Effects on Kidney Structure, Blood Pressure and Urinary Sodium Excretion in Adult Offspring

“…As previously demonstrated [7,28], this higher expression of TGF-β1, a major inducer of EMT in epithelial cells [37], could be associated with decreased expression of EMT-inducing transcriptional factor [38,39,40], which in turn, upregulated fibronectin and collagen renal expression, proteins being considered mesenchymal markers. The production of interstitial matrix compounds suggests that podocytes have adapted a mesenchymal phenotype in maternal tobacco exposure offspring, which could profoundly change their functions [41,42].…”

“…These adaptations may be beneficial in the short term, but may have adverse consequences in postnatal life [1]. Fetal programming by different insults results in low birth weight and reduction in nephron number [2,3,4,5,6,7], and increases the risk for adult development of cardiovascular and renal diseases [4,5,6]. Low birth weight (LBW) is also associated with impaired renal growth, raised blood pressure and impaired renal function [8,9,10,11].…”

Effect of intracerebroventricular epinephrine microinjection on blood pressure and urinary sodium handling in gestational protein-restricted rat adult male offspring

“…Environmental and genetic factors influence the ontogenetic development, and on adverse circumstance, eventually leading to functional and structural disorders of tissues and organs. In rats, gestational protein restriction is associated with low birthweight, fewer nephrons, and increased risk for the development of heart diseases, kidney dysfunction and metabolic syndrome in adult life [1][2][3][4][5][6][7]. We recently demonstrated that maternal low-protein (LP) intake offspring have a lower birth weight, 30% fewer nephrons, and arterial hypertension [3,4,6] when compared with age-matched, normal (NP) protein intake group.…”

“…We recently demonstrated that maternal low-protein (LP) intake offspring have a lower birth weight, 30% fewer nephrons, and arterial hypertension [3,4,6] when compared with age-matched, normal (NP) protein intake group. Additionally, water and salt balance studies have shown that hypertension in LP offspring is associated with decreased urinary sodium excretion [3][4][5][6][7][8]. The involvement of the central nervous system (CNS) in the control of blood pressure and, water and salt homeostasis has been demonstrated in several studies [9][10][11][12].…”