title: The polysaccharide fraction of Propionibacterium acnes modulates the development of experimental focal segmental glomerulosclerosis.
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-β, 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 α-smooth muscle actin (α-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 α-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.
authors.affiliation: Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Vanessa Oliveira
authors.initials: VO
authors.lastname: Reis
authors.forename: Janice Costa
authors.initials: JC
authors.lastname: Silva
authors.forename: Gabriela Trindade
authors.initials: GT
authors.lastname: Souza
authors.forename: Patricia
authors.initials: P
authors.lastname: Semedo
authors.forename: Bruna
authors.initials: B
authors.lastname: Buscariollo
authors.forename: Rafael Luiz
authors.initials: RL
authors.lastname: Pereira
authors.forename: Marcos Antonio
authors.initials: MA
authors.lastname: Cenedeze
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pacheco-Silva
authors.forename: Ieda M
authors.initials: IM
authors.lastname: Longo-Maugéri
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
authors.forename: Alexandre Castro
authors.initials: AC
authors.lastname: Keller
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005355:Fibrosis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000209:etiology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D011425:Propionibacterium acnes / Q000737:chemistry*; D020011:Protective Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy; D051437:Renal Insufficiency / Q000139:chemically induced / Q000188:drug therapy; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D011135:Polysaccharides, Bacterial; D020011:Protective Agents; D004317:Doxorubicin