Abstract

The apoptosis of glomerular mesangial cells (GMC) in rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis, is accompanied by sublytic C5b-9 deposition, but the mechanism of sublytic C5b-9-mediated GMC apoptosis has not been elucidated. In the present study, the gene expression profiles both in the GMC stimulated by sublytic C5b-9 and the rat renal tissue of Thy-1N were detected using microarrays. Among the co-up-regulated genes, the up-regulation of interferon regulatory factor-1 (IRF-1) was further confirmed. Increased caspase 8 and caspase 3 expression and caspase 8 promoter activity in the GMC were also identified. Meanwhile, overexpression or knockdown of IRF-1 not only enhanced or inhibited GMC apoptosis and caspase 8 and 3 induction but also increased or decreased caspase 8 promoter activity, respectively. The element of IRF-1 binding to the caspase 8 promoter was first revealed. Furthermore, silencing IRF-1 or repressing the activation of caspases 8 and 3 significantly reduced GMC apoptosis, including other pathologic changes of Thy-1N. These novel findings indicate that GMC apoptosis of Thy-1N is associated with the IRF-1-activated caspase 8 pathway.

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Authors

Liu L, Qiu W, Wang H, Li Y, Zhou J, Xia M, Shan K, Pang R, Zhou Y, Zhao D, Wang Y

Institution

Department of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, China.

Source

The Journal of biological chemistry 287:20 2012 May 11 pg 16410-23

MeSH

Animals
Apoptosis
Caspase 3
Caspase 8
Cell Line
Complement Membrane Attack Complex
Disease Models, Animal
Enzyme Activation
Glomerulonephritis, Membranoproliferative
Humans
Interferon Regulatory Factor-1
Isoantibodies
Mesangial Cells
Rats
Response Elements

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22427665