Cellular cholesterol modifies flow mediated gene expression.

Cellular cholesterol modifies flow mediated gene expression. Am J Physiol Renal Physiol. 2019 Jul 31;: Authors: Repetti RL, Meth J, Sonubi O, Flores D, Satlin LM, Rohatgi R Abstract Downregulation of heme oxygenase-1 (HO1), cyclooxygenase-2 (COX2), and nitric oxide synthase-2 (NOS2) in kidney of Dahl rodents causes salt sensitivity while restoring their expression aids in sodium excretion and blood pressure reduction. Loading cholesterol into collecting duct (CD) cells represses fluid shear stress (FSS) mediated COX2 activity. Thus, we hypothesized that cholesterol represses flow responsive genes necessary to effectuate sodium excretion. To this end, CD cells were used to test whether FSS induces these genes and if cholesterol loading represses them. Mice fed either 0% or 1% cholesterol diet were injected with saline, urine volume and electrolytes measured, and renal gene expression determined FSS exposed CD cells showed increases of HO1 mRNA by 350-, COX2 by 25-, and NOS2 by 8-fold in sheared (p<0.01) compared to static cells. Immunoblotting of sheared cells showed increases in HO1, COX2 and NOS2 protein, while conditioned media contained more HO1 and PGE2 than static cells. Cholesterol loading repressed the sheared mediated protein abundance of HO1 and NOS2, and HO1 and PGE2 concentrations in media. In cholesterol fed mice, urine volume was less at 6 hrs after injection of isotonic saline (p<0.05). Urinary [Na], [K] and osmol...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research