Absence of nicotinic acetylcholine receptor a7 subunit amplifies inflammation and accelerates onset of fibrosis: An inflammatory kidney model

Luan Truong, Jessica Trostel, Gabriela E. Garcia

Research output: Contribution to journalArticle

20 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)3558-3570
Number of pages13
JournalFASEB Journal
Volume29
Issue number8
DOIs
StatePublished - Aug 1 2015

Keywords

  • Chemokines
  • Cytokines
  • Macrophages

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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