TY - JOUR
T1 - Absence of nicotinic acetylcholine receptor a7 subunit amplifies inflammation and accelerates onset of fibrosis
T2 - An inflammatory kidney model
AU - Truong, Luan
AU - Trostel, Jessica
AU - Garcia, Gabriela E.
N1 - Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Inflammation is regulated by endogenous mechanisms, including anti-inflammatory cytokines, adenosine, and the nicotinic acetylcholine receptor α7 subunit (α7nAChR). We investigated the role of α7nAChR in protection against the progression of tissue injury in amodel of severe, macrophage-mediated, cytokine-dependent antiglomerular basement membrane (GBM) glomerulonephritis (GN), in α7nAChR-deficient (α7-/-) mice . At d 7 after the injection of anti-GBM antibody, kidneys from α7-/- mice displayed severe glomeruli (P < 0.0001) and tubulointerstitial lesions (P < 0.001) compared to kidneys fromWTmice. An important finding was the presence of severe glomerulosclerosis in α7-/- mice in this early phase of the disease. Kidneys of α7-/- mice showed greater accumulation of inflammatory cells and higher expression of chemokines and cytokines than did those of WT mice. In addition, in α7-/- fibrotic kidneys, the expression of fibrin, collagen, TGF-β, and tissue inhibitor of metalloproteinase (TIMP)-2 increased, and the expression of TIMP3 declined. The increase in counterregulatory responses to inflammation in α7-/- nephritic kidneys did not compensate for the lack of α7nAChR. These findings indicate that α7nAChR plays a key role in regulating the inflammatory response in anti- GBM GN and that disruption of the endogenous protective α7nAChR amplifies inflammation to accelerate kidney damage and fibrosis.-Truong, L. D., Trostel. J., Garcia, G. E. Absence of nicotinic acetylcholine receptor α7 subunit amplifies inflammation and accelerates onset of fibrosis: An inflammatory kidney model.
AB - Inflammation is regulated by endogenous mechanisms, including anti-inflammatory cytokines, adenosine, and the nicotinic acetylcholine receptor α7 subunit (α7nAChR). We investigated the role of α7nAChR in protection against the progression of tissue injury in amodel of severe, macrophage-mediated, cytokine-dependent antiglomerular basement membrane (GBM) glomerulonephritis (GN), in α7nAChR-deficient (α7-/-) mice . At d 7 after the injection of anti-GBM antibody, kidneys from α7-/- mice displayed severe glomeruli (P < 0.0001) and tubulointerstitial lesions (P < 0.001) compared to kidneys fromWTmice. An important finding was the presence of severe glomerulosclerosis in α7-/- mice in this early phase of the disease. Kidneys of α7-/- mice showed greater accumulation of inflammatory cells and higher expression of chemokines and cytokines than did those of WT mice. In addition, in α7-/- fibrotic kidneys, the expression of fibrin, collagen, TGF-β, and tissue inhibitor of metalloproteinase (TIMP)-2 increased, and the expression of TIMP3 declined. The increase in counterregulatory responses to inflammation in α7-/- nephritic kidneys did not compensate for the lack of α7nAChR. These findings indicate that α7nAChR plays a key role in regulating the inflammatory response in anti- GBM GN and that disruption of the endogenous protective α7nAChR amplifies inflammation to accelerate kidney damage and fibrosis.-Truong, L. D., Trostel. J., Garcia, G. E. Absence of nicotinic acetylcholine receptor α7 subunit amplifies inflammation and accelerates onset of fibrosis: An inflammatory kidney model.
KW - Chemokines
KW - Cytokines
KW - Macrophages
UR - http://www.scopus.com/inward/record.url?scp=84940416772&partnerID=8YFLogxK
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U2 - 10.1096/fj.14-262493
DO - 10.1096/fj.14-262493
M3 - Article
C2 - 25985801
AN - SCOPUS:84940416772
SN - 0892-6638
VL - 29
SP - 3558
EP - 3570
JO - FASEB Journal
JF - FASEB Journal
IS - 8
ER -