Association of OSR‐1 With Vascular Dysfunction and Hypertension in Polycystic Kidney Disease

Abstract

Autosomal‐dominant polycystic kidney disease (ADPKD) is associated with oxidative stress and hypertension development before renal function decline and cardiovascular disease development. Oxidative stress‐responsive kinase‐1 (OSR‐1) participates in the signaling regulating Na+ transport during oxidative stress and also plays a role in the regulation of cell volume and blood pressure. Therefore, we aimed to investigate the potential role of OSR‐1 in ADPKD patients. Eighty ADPKD patients, 80 healthy controls, and 80 non‐ADPKD patients with hypertension were enrolled in this cross‐sectional study. Twenty‐four‐hour ambulatory blood pressure monitoring was conducted in all participants. Blood samples were taken after 12‐h fasting for the measurement of biochemical parameters and OSR‐1 gene expression. Vascular dysfunction was assessed using ischemia‐induced forearm flow‐mediated vasodilation (FMD). Briefly, of the 80 ADPKD patients, 41(51%) were male, and 53(66%) of them were hypertensive. The mean age of the 80 controls was 35.3 ± 12.6 years, and 37(46%) of them were male. The mean age of the 80 non‐ADPKD patients with hypertension was 44.6 ± 11.9 years, and 38(47.5) of them were male. There were significant differences in serum OSR‐1 gene expression between the ADPKD patients and the control subjects. Serum OSR‐1 gene expression was also significantly increased in hypertensive ADPKD patients in comparison with both normotensive ADPKD counterparts and non‐ADPKD hypertensive subjects. Serum OSR‐1 gene expression was increased in patients with ADPKD than healthy subjects. Low estimated glomerular filtration rate (eGFR), OSR‐1 gene expression, total kidney volume (TKV), and high‐density lipoprotein (HDL) were also independently associated with hypertension in ADPKD patients.

Oxidative Stress in the Pathogenesis and Evolution of Chronic Kidney Disease: Untangling Ariadne’s Thread

“…Oxidative stress-responsive kinase-1 (OSR-1), which is associated with regulation of Na + transport and cell volume during oxidative stress, has recently been shown to play a role in the regulation of blood pressure in ADPKD [139]. Thus, serum OSR-1 gene expression has been found to be significantly increased in hypertensive ADPKD patients in comparison with normotensive ADPKD counterparts, non-ADPKD hypertensive subjects, as well as healthy individuals [139].…”

CircNRIP1 KNOCKDOWN ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED HUMAN KIDNEY 2 CELL APOPTOSIS AND INFLAMMATION THROUGH miR-339-5p/OXSR1 PATHWAY

“…OXSR1 contributes to hepatocellular carcinoma cell proliferation and motility by interacting with miR-186-5p as well as LINC01291 (32). Another study showed that OXSR1 expression was associated with vascular dysfunction and hypertension in autosomal-dominant polycystic kidney disease (33). In particular, OXSR1 depletion has a protective effect on the kidney of septic rats and its overexpression relieves miR-93-5p–induced inhibitory effects in LPS-treated HK2 cells (17,34).…”