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Abstract MP31: A20 In Renal Tubular Cells Protects Against Hypertension

Publication ,  Conference
Lu, X; Ren, J; Griffiths, R; Hammer, G; Yang, T; Crowley, SD
Published in: Hypertension
September 2021

The ubiquitin-editing protein A20 suppresses NF-κB signaling, which contributes to hypertension and kidney inflammation. However, whether A20 generated directly in the kidney tubule regulates blood pressure requires elucidation. To examine the role of tubular A20 in hypertension, we bred mice with the Pax8-rtTA and Tet-On lines to generate inducible renal epithelial cell A20 knockout mice (A20 iKKO). Mice with all 3 transgenes were used as the A20 iKKO group, while mice lacking the Pax8-rtTA or Tet-On transgene acted as wild-type (WT) controls. Prior to experiments, all mice were given 2mg/ml of doxycycline in the drinking water for 2 weeks to ablate A20 in renal tubular cells. By qPCR, mRNA levels for A20 were selectively reduced by 63% in A20 iKKO kidneys vs WT controls. Baseline blood pressures were similar in the groups. During 3 weeks of chronic angiotensin (Ang) II infusion (500ng/kg/min), A20 iKKO mice exhibited higher mean arterial pressures measured by telemetry compared to WTs (155±2 vs. 143±4 mmHg; =0.024). As a result, the A20 iKKOs had worse cardiac hypertrophy than the WTs after AngII (7.10±0.17 vs. 6.27±0.16 mg heart/g body weight; <0.005.). In addition, mRNA levels for TNF-α were markedly increased (1.54±0.21 vs. 1.0±0.1 arbitrary units; <0.05) in A20 iKKO kidneys compared to WTs, whereas the genes encoding IL-1β and IFNγ were similarly expressed in the groups. In the 3 week of AngII, levels of sodium-hydrogen exchanger 3 (NHE3) protein (1.50±0.10 vs. 1.0±0.1; <0.0005) and NF-κB p50 subunit mRNA (1.30±0.14 vs. 1.0±0.06; <0.05) were increased in A20 iKKO kidneys compared to WTs. Treating both WTs and A20 iKKOs with the TNF-α inhibitor (R7050, 12mg/body weight) every other day during the 1 week of AngII infusion yielded similar levels of blood pressure elevation (141.57±4.54 vs. 140.35±5.60 mmHg; =0.87). These data suggest that tubular A20 limits sodium reabsorption and blood pressure elevation by inhibiting NF-κB/ TNF-dependent NHE3 induction in the kidney.

Duke Scholars

Published In

Hypertension

DOI

EISSN

1524-4563

ISSN

0194-911X

Publication Date

September 2021

Volume

78

Issue

Suppl_1

Publisher

Ovid Technologies (Wolters Kluwer Health)

Related Subject Headings

  • Cardiovascular System & Hematology
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1117 Public Health and Health Services
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

APA
Chicago
ICMJE
MLA
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Lu, X., Ren, J., Griffiths, R., Hammer, G., Yang, T., & Crowley, S. D. (2021). Abstract MP31: A20 In Renal Tubular Cells Protects Against Hypertension. In Hypertension (Vol. 78). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1161/hyp.78.suppl_1.mp31
Lu, Xiaohan, Jiafa Ren, Robert Griffiths, Gianna Hammer, Ting Yang, and Steven D. Crowley. “Abstract MP31: A20 In Renal Tubular Cells Protects Against Hypertension.” In Hypertension, Vol. 78. Ovid Technologies (Wolters Kluwer Health), 2021. https://doi.org/10.1161/hyp.78.suppl_1.mp31.
Lu X, Ren J, Griffiths R, Hammer G, Yang T, Crowley SD. Abstract MP31: A20 In Renal Tubular Cells Protects Against Hypertension. In: Hypertension. Ovid Technologies (Wolters Kluwer Health); 2021.
Lu, Xiaohan, et al. “Abstract MP31: A20 In Renal Tubular Cells Protects Against Hypertension.” Hypertension, vol. 78, no. Suppl_1, Ovid Technologies (Wolters Kluwer Health), 2021. Crossref, doi:10.1161/hyp.78.suppl_1.mp31.
Lu X, Ren J, Griffiths R, Hammer G, Yang T, Crowley SD. Abstract MP31: A20 In Renal Tubular Cells Protects Against Hypertension. Hypertension. Ovid Technologies (Wolters Kluwer Health); 2021.

Published In

Hypertension

DOI

EISSN

1524-4563

ISSN

0194-911X

Publication Date

September 2021

Volume

78

Issue

Suppl_1

Publisher

Ovid Technologies (Wolters Kluwer Health)

Related Subject Headings

  • Cardiovascular System & Hematology
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1117 Public Health and Health Services
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology