MicroRNA-195a-5p Regulates Blood Pressure by Inhibiting NKCC2A

Abstract

BACKGROUND: Previous studies showed that miR-195a-5p was among the most abundant miRNAs expressed in the kidney. METHODS: Lentivirus silencing of tumor necrosis factor-α (TNF) was performed in vivo and in vitro. Luciferase reporter assays confirmed that bumetanide-sensitive Na + -K + -2Cl − cotransporter isoform A (NKCC2A) mRNA is targeted and repressed by miR-195a-5p. Radiotelemetry was used to measure mean arterial pressure. RESULTS: TNF upregulates mmu-miR-195a-5p, and -203 and downregulates mmu-miR-30c and -100 in the medullary thick ascending limb of male mice. miR-195a-5p was >3-fold higher in the renal outer medulla of mice given an intrarenal injection of murine recombinant TNF, whereas silencing TNF inhibited miR-195a-5p expression by ≈51%. Transient transfection of a miR-195a-5p mimic into medullary thick ascending limb cells suppressed NKCC2A mRNA by ≈83%, whereas transfection with Anti-miR-195a-5p increased NKCC2A mRNA. Silencing TNF in medullary thick ascending limb cells prevented increases in miR-195 induced by 400 mosmol/kg H 2 O medium, an effect reversed by transfection with a miR-195a-5p mimic. Expression of phosphorylated NKCC2 increased 1.5-fold in medullary thick ascending limb cells transfected with Anti-miR-195a-5p and a miR-195a-5p mimic prevented the increase, which was induced by silencing TNF in cells exposed to 400 mosmol/kg H 2 O medium after osmolality was increased by adding NaCl. Intrarenal injection of TNF suppressed NKCC2A mRNA, whereas injection of miR-195a-5p prevented the increase of NKCC2A mRNA abundance and phosphorylated NKCC2 expression when TNF was silenced. Intrarenal injection with miR-195a-5p markedly attenuated MAP after renal silencing of TNF in mice given 1% NaCl. CONCLUSIONS: The study identifies miR-195a-5p as a salt-sensitive and TNF-inducible miRNA that attenuates NaCl-mediated increases in blood pressure by inhibiting NKCC2A.

Association between Resistant Arterial Hypertension, Type 2 Diabetes, and Selected microRNAs

“…TNF increases MIR195a-5p expression, which in turn interacts with the 3 ′ UTR of NKCCA2 to regulate NaCl excretion. This attenuates NaCl-induced increases in blood pressure [15]. One of the most common complications of improperly controlled AH (RAH) is cardiac hypertrophy.…”

Effect of RNA interference with HIF-1α on the growth of pulmonary artery endothelial cells in broiler chickens

“…It has been reported in the literature that interfering lentivirus targeting STAT3, after infiltrating SW1990 cells, successfully achieved silencing STAT3 gene, which led to a decrease in the expression of MMP-2 and VEGF proteins related to tumor invasion and metastasis, and ultimately reduced the invasive ability of pancreatic cancer cells ( Yang et al, 2009 ). It has also been reported that TNF interference by lentivirus significantly inhibited the expression of miR-195a-5p to inhibit NKCC2A to attenuate NaCl-mediated blood pressure elevation ( Hao et al, 2023 ). It is clear that RNA interference is a robust tool for mechanistic research on diseases, but few reports of RNA interference and broiler ascites syndrome have been reported.…”