The polysaccharide fraction of Propionibacterium acnes modulates the development of experimental focal segmental glomerulosclerosis

The polysaccharide fraction of Propionibacterium acnes modulates the development of experimental focal segmental glomerulosclerosis

Author Reis, Vanessa Oliveira Autor UNIFESP Google Scholar
Silva, Janice Costa Autor UNIFESP Google Scholar
Souza, Gabriela Trindade Autor UNIFESP Google Scholar
Semedo, Patricia Autor UNIFESP Google Scholar
Buscariollo, Bruna Autor UNIFESP Google Scholar
Pereira, Rafael Luiz Autor UNIFESP Google Scholar
Cenedeze, Marcos Antonio Autor UNIFESP Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Longo-Maugeri, Ieda M. Autor UNIFESP Google Scholar
Saraiva Camara, Niels Olsen Autor UNIFESP Google Scholar
Keller, Alexandre Castro Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Inst Israelita Ensino & Pesquisa Albert Einstein
Universidade de São Paulo (USP)
Abstract The pathogenesis of focal segmental glomerulosclerosis (FSGS) appears to be associated with type-2 cytokines and podocyte dysfunction. in this study, we tested the hypothesis that immunization with the polysaccharide fraction of Propionibacterium acnes (PS), a pro-Th1 agonist, may subvert the type-2 profile and protect podocytes from adriamycin-induced glomerulosclerosis. Adriamycin injection resulted in albuminuria and increased serum creatinine in association with loss of glomerular podocin and podoplanin expression, which is consistent with podocyte dysfunction. Renal tissue analysis revealed the expression of transcripts for GATA3 and fibrogenic-related proteins, such as TGF-beta, tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase 9 (MMP9). in association with the expression of fibrogenic transcripts, we observed peri-glomerular expression of a-smooth muscle actin (alpha-SMA), indicating epithelial-to-mesenchymal transition, and increased expression of proliferating cell nuclear antigen (PCNA) in tubular cells, suggesting intense proliferative activity. Previous immunization with PS inhibited albuminuria and serum creatinine in association with the preservation of podocyte proteins and inhibition of fibrogenic transcripts and the expression of alpha-SMA and PCNA proteins. Tissue analysis also revealed that PS treatment induced expression of mRNA for GD3 synthase, which is a glycosiltransferase related to the synthesis of GD3, a ganglioside associated with podocyte physiology. in addition, PS treatment inhibited the influx of inflammatory CD8(pos) and CD11b(pos) cells to kidney tissue. Finally, PS treatment on day 4 post-ADM, a period when proteinuria was already established, was able to improve renal function. Thus, we demonstrate that the PS fraction of P. acnes can inhibit FSGS pathogenesis, suggesting that immunomodulation can represent an alternative approach for disease management. (C) 2011 Elsevier GmbH. All rights reserved.
Keywords Adriamycin nephropathy
FSGS
Glomerulosclerosis
Immunomodulation
Propionibacterium acnes
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2007/07120-0
CNPq: 501848/2009-6
CNPq: 484445/2010-3
Date 2012-09-01
Published in Immunobiology. Jena: Elsevier Gmbh, Urban & Fischer Verlag, v. 217, n. 9, p. 831-841, 2012.
ISSN 0171-2985 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 831-841
Origin http://dx.doi.org/10.1016/j.imbio.2011.12.003
Access rights Closed access
Type Article
Web of Science ID WOS:000309016700001
URI http://repositorio.unifesp.br/handle/11600/35226

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