Dataset Information


Absence of nicotinic acetylcholine receptor α7 subunit amplifies inflammation and accelerates onset of fibrosis: an inflammatory kidney model.

ABSTRACT: 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 a model of severe, macrophage-mediated, cytokine-dependent anti-glomerular 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 from WT mice. 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.


PROVIDER: S-EPMC4511204 | BioStudies | 2015-01-01


REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6458176 | BioStudies
2013-01-01 | S-EPMC3575386 | BioStudies
2014-01-01 | S-EPMC4055015 | BioStudies
1000-01-01 | S-EPMC2689902 | BioStudies
2018-01-01 | S-EPMC6028598 | BioStudies
2019-01-01 | S-EPMC6475388 | BioStudies
2015-01-01 | S-EPMC4380454 | BioStudies
2014-03-26 | E-GEOD-55808 | ArrayExpress
1000-01-01 | S-EPMC441434 | BioStudies
2015-01-01 | S-EPMC4664719 | BioStudies