MicroRNA-133a-Dependent Inhibition of Proximal Tubule Angiotensinogen by Renal TNF (Tumor Necrosis Factor)
| Autor: | Hong Zhao, Nicholas R. Ferreri, Joseph Salzo, Zbigniew Darzynkiewicz, Mary Hao, Shoujin Hao |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Angiotensinogen Blood Pressure 030204 cardiovascular system & hematology Kidney Article law.invention Kidney Tubules Proximal 03 medical and health sciences 0302 clinical medicine law Internal medicine parasitic diseases microRNA Internal Medicine medicine Animals Gene silencing Sodium Chloride Dietary Messenger RNA biology Tumor Necrosis Factor-alpha Chemistry biology.organism_classification Mice Inbred C57BL MicroRNAs 030104 developmental biology Endocrinology Blood pressure medicine.anatomical_structure Gene Expression Regulation Lentivirus Recombinant DNA RNA Interference Tumor necrosis factor alpha |
| Zdroj: | Hypertension |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.120.15435 |
| Popis: | We showed that intrarenal suppression of TNF (tumor necrosis factor) production under low salt (LS) conditions increases renal cortical AGT (angiotensinogen) mRNA and protein expression. Intrarenal injection of murine recombinant TNF attenuated increases of AGT in mice ingesting LS. Moreover, AGT mRNA and protein expression increased ≈6-fold and 2-fold, respectively, in mice ingesting LS that also received an intrarenal injection of a lentivirus construct that specifically silenced TNF in the kidney (U6-TNF-ex4). Silencing of TNF under normal salt and high salt (HS) conditions also resulted in increased AGT expression. Since renal TNF production decreases in response to LS and increases in response to HS, the data suggest that alterations in TNF production under these conditions modulate the degree of AGT expression. We also tested the hypothesis that TNF inhibits intrarenal AGT expression by a mechanism involving miR-133a. Expression of miR-133a decreased in mice given LS and increased in response to HS for 7 days. Intrarenal silencing of TNF reversed the effects of HS on miR-133a-dependent AGT expression. In contrast, intrarenal TNF administration increased miR-133a expression in the kidney. Collectively, the data suggest that miR-133a is a salt-sensitive microRNA that inhibits AGT in the kidney and is increased by TNF. The HS-induced increase in blood pressure observed following silencing of TNF was markedly reduced upon intrarenal administration of miR-133a suggesting that intrinsic effects of TNF in the kidney to limit the blood pressure response to HS include an increase in miR-133a, which suppresses AGT expression. |
| Databáze: | OpenAIRE |
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