Abstract: SA-PO1080

β-Catenin Activity Is Dependent on Mouse Strain in Angiotensin II Induced Renal Hypertensive Injury

Session Information

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Kulatilake, Priyantha Sumudhu, University of Bristol, Bristol, United Kingdom
  • Wolodimeroff, Elena, University of Bristol, Bristol, United Kingdom
  • Williams, Helen, University of Bristol, Bristol, United Kingdom
  • Higgins, Sarah, University of Bristol, Bristol, United Kingdom
  • May, Carl J., University of Bristol, Bristol, United Kingdom
  • Welsh, Gavin Iain, University of Bristol, Bristol, United Kingdom
  • George, Sarah J., University of Bristol, Bristol, United Kingdom
Background

Hypertensive kidney injury has been well established; however, little is known about the involvement of Wnt/β-catenin signalling in this process. Here, we induced hypertension with Angiotensin II (AngII) infusion in two strains of mice to determine the effect on β-catenin activity and renal physiology.

Methods

DBA2/J (DBA) mice and mice crossed on a C57/Bl6x129S1/SvImJ background (129/Bl6) were implanted with subcutaneous osmotic pumps containing AngII for 28 days. Blood pressures (BP) were measured and kidneys were excised and processed for RNA, protein and histological analysis.

Results

At baseline DBA mice were significantly more proteinuric than 129/Bl6 mice (n=8 p<0.05). However, AngII infusion increased mean arterial BP and albuminuria in both strains of mice (n=8 p<0.01). This confirmed AngII induced hypertensive kidney injury. We observed significant changes in renovascular remodelling in both strains with AngII infusion. Increased renovascular fibrosis was induced with AngII in DBA mice (n=8 p<0.05); however, it was reduced 129/Bl6 mice (n=8 p<0.05). Interestingly, only 129/Bl6 mice developed generalised renal cortical fibrosis with AngII infusion (n=8 p<0.05). Levels of active β-catenin only significantly increased in DBA mice that received AngII (n=8 p<0.01) and immunohistochemistry showed a renal tubular distribution of β-catenin in kidney paraffin sections. A Wnt focused microarray showed increased β-catenin pathway signalling with altered downstream cell cycling markers. In vitro work showed that β-catenin blockade with 25µM iCRT resulted in decreased proliferation (n=3 p<0.05) and increased permeability (n=3 p<0.05) of HK-2 cells (proximal tubular).

Conclusion

Firstly; these results suggest β-catenin activity in renal hypertension is strain dependent. Secondly; that β-catenin plays an important role in proximal tubular cell proliferation and permeability; therefore β-catenin activity could prove to be a mechanism by which proteinuria develops in DBA mice with AngII induced hypertension.