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Regulation of Formyl Peptide Receptor 2 During Chronic Kidney Disease
Author(s) -
Labes Robert,
Neymeyer Hanna,
Saez Fara,
Reverte Virginia,
Salazar Javier,
Bachmann Sebastian,
Paliege Alexander
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.663.12
Subject(s) - myofibroblast , kidney disease , inflammation , fibrosis , kidney , receptor , medicine , immunohistochemistry , pathology , annexin a1 , endocrinology , biology , annexin , staining
The G‐protein coupled receptor formyl peptide receptor 2 (FPR2) integrates signals of multiple anti‐inflammatory and anti‐fibrotic mediators including lipoxin A4, resolvin D1, and annexin A1. Previous studies have demonstrated protective effects of FPR2 in animal models of renal disease but the localization of FPR2 in the healthy kidney and its regulation in chronic kidney disease (CKD) have not been elucidated. Aim of this study was to determine the renal localization of FPR2 under control conditions and in a rat model of CKD. Newborn rats were treated with the AT1R antagonist Candesartan from postnatal d1‐14 to impair nephrogenesis and examined at 11 moth of age (CKD rats). Expression of FPR2 was studied using immunohistochemistry (IHC) and double labeling immunofluorescence (IF) for FPR2 and markers for fibroblasts, myofibroblasts, macrophages, and endothelial cells. CKD rats showed signs of renal inflammation and fibrosis with a focal accumulation of macrophages, myofibroblasts and extracellular matrix components. IHC revealed expression of FPR2 in the tubulointerstitium of controls and a strong accumulation of FPR2 expressing cells in fibrotic areas of CKD animals. IF identified fibroblasts and endothelial cells as the predominant FPR2 expressing cell types in both groups. Abundant signal was further detected in macrophages and myofibroblasts in the fibrotic areas of CKD animals. Our results show that FPR2 is abundantly expressed in the kidneys of control and CKD animals. It may therefore play an important role in the regulation of normal renal function and exert anti‐inflammatory and anti‐fibrotic effects during CKD. FPR2 may thus provide a promising target for pharmacological intervention in the treatment of CKD.