In: Scientific Reports, 2019, vol. 9, no. 1, p. 1–16
In proteinuric nephropathies of chronic kidney disease, the epithelial cells of the nephron including the collecting duct are exposed to high concentrations of luminal albumin. Albumin is taken up from collecting duct cells by endocytosis causing excessive reactive oxygen species (ROS) production and a proinflammatory response. Curcumin used in the traditional medicine possesses...
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In: Journal of Cellular and Molecular Medicine, 2019, vol. 23, no. 10, p. 6543–6553
The NPHS2 gene, encoding the slit diaphragm protein podocin, accounts for genetic and sporadic forms of nephrotic syndrome (NS). Patients with NS often present symptoms of volume retention, such as oedema formation or hypertension. The primary dysregulation in sodium handling involves an inappropriate activation of the epithelial sodium channel, ENaC. Plasma proteases in a...
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In: Journal of the American Heart Association, 2018, p. -
In pregnancy, a high plasma volume maintains uteroplacental perfusion and prevents placental ischemia, a condition linked to elevated maternal blood pressure (BP). Reducing BP by increasing Na+ intake via plasma volume expansion appears contra‐ intuitive. We hypothesize that an appropriate Na+ intake in pregnancy reduces maternal BP and adapts the renin‐angiotensin system in a...
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In: Scientific Reports, 2017, vol. 7, no. 1, p. 4149
Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins...
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In: Journal of the American Society of Nephrology, 2016, p. -
Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a...
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In: Journal of the American Society of Nephrology, 2016, vol. 27, no. 3, p. 731–744
Albuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per...
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In: American Journal of Physiology - Renal Physiology, 2015, p. -
The balance between vasoconstrictor/sodium retaining and vasodilator/natriuretic systems is essential for maintaining body fluid and electrolyte homeostasis. Natriuretic peptides, such as atrial natriuretic protein (ANP) belong to the vasodilator/natriuretic system. ANP is produced by the conversion of pro-ANP into ANP which is achieved by a proteolytical cleavage executed by corin. In the...
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In: Journal of the American Society of Nephrology, 2014, p. ASN.2014020148
Transepithelial water flow across the renal proximal tubule is mediated predominantly by aquaporin-1 (AQP1). Along this nephron segment, luminal delivery and transepithelial reabsorption are directly coupled, a phenomenon called glomerulotubular balance. We hypothesized that the surface expression of AQP1 is regulated by fluid shear stress, contributing to this effect. Consistent with this...
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In: Kidney International, 2012, p. -
Severe sepsis is often accompanied by acute renal failure with renal tubular dysfunction. Albuminuria is a common finding in septic patients and we studied whether it was due to an impairment of proximal tubular endocytosis of filtered albumin. We studied the regulation of megalin and cubilin, the two critical multiligand receptors responsible for albumin absorption, during severe experimental...
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In: The American Journal of Pathology, 2011, vol. 179, no. 5, p. 2177–2188
In many kidney diseases, the original insult primarily involves the glomerulus and may then pass onto the tubulointerstitium. Several hypotheses link glomerular disease to tubular injury; perhaps the foremost hypothesis involves chronic tubular hypoxia. The reported effects of hypoxia and consecutive stabilization of hypoxia-inducible factors (HIFs), however, are controversial. Hypoxia induces...
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