RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm.
Kidney Int
; 87(4): 771-83, 2015 Apr.
Article
in En
| MEDLINE
| ID: mdl-25469849
ABSTRACT
Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 min injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 min unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury, blood flow was decreased in the inner cortex of wild-type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild-type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18 h after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (VSMCs) to secrete the macrophage chemoattractant RANTES, a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating Gα protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMC-specific RGS4 knockout showing high macrophage density by T2 MRI compared with transgenic and non-transgenic mice after the 10 min injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC, inhibits angiotensin II-mediated cytokine signaling and macrophage recruitment during reperfusion, distinct from vasomotor regulation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vasoconstriction
/
Angiotensin II
/
Reperfusion Injury
/
RGS Proteins
/
Myocytes, Smooth Muscle
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Kidney Cortex
Limits:
Animals
/
Humans
Language:
En
Journal:
Kidney Int
Year:
2015
Type:
Article
Affiliation country:
United States