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-ß, 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.
Subject(s)
Glomerulosclerosis, Focal Segmental/etiology , Polysaccharides, Bacterial/pharmacology , Propionibacterium acnes/chemistry , Protective Agents/pharmacology , Animals , Cell Proliferation/drug effects , Disease Models, Animal , Doxorubicin/adverse effects , Epithelial-Mesenchymal Transition/drug effects , Fibrosis/genetics , Gene Expression Regulation/drug effects , Glomerulosclerosis, Focal Segmental/drug therapy , Kidney Glomerulus/drug effects , Kidney Glomerulus/pathology , Male , Mice , Mice, Inbred BALB C , Polysaccharides, Bacterial/administration & dosage , Polysaccharides, Bacterial/isolation & purification , Protective Agents/administration & dosage , Protective Agents/isolation & purification , Proteinuria/drug therapy , Renal Insufficiency/chemically induced , Renal Insufficiency/drug therapy , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism , Transcription, GeneticABSTRACT
O álcool, que de início, faz parte de grandes cerimônias, festas, encontros de amigos, atualmente vem se transformando numa questäo preocupante porque o número de mulheres, que fazem consumo de bebidas alcoólicas aumentou, e consequentemente, o número de gestantes. Considerando-se que näo somente o organismo materno como também o do ser em desenvolvimento estäo sujeitos às alteraçöes metabólicas, inevitavelmente, tornar-se-äo alvos das modificaçöes induzidas pelo alcoól. Durante o desenvolvimento humano é importante levar em consideraçäo a época gestacional, já que, dependendo do estágio, o indivíduo fica susceptível aos agentes teratogenos. O presente trabalho pretende dar uma pequena contribuiçäo perante este problema social, trazendo o conhecimento da açäo do álcool no embriäo e no feto, suas respectivas alteraçöes, desde a de menor gravidade (irritabilidade, falta de atençäo, deficiência no desempenho motor e outros) até a Síndrome Alcoólica Fetal (SAF) e também procura analisar o grau de conhecimento da populaçäo sobre as consequências da açäo do alcoól no organismo da mulher grávida e as possíveis alteraçöes que poderäo ocorrer com o feto. Para que essa análise fosse possível, foram realizadas entrevistas através de formulários aplicados em amostras populacionais das regiöes Norte, Oeste, Sul e Baixada Fluminense, aproximadamente 100 pessoas por regiäo. Visitamos também algumas Instituiçöes públicas e privadas (23), entrevistando Enfermeiras no setor de Pediatria, no intuito de detectar as dificuldades encontradas em relaçäo ao diagnóstico e à conduta frente a Síndrome Alcoólica Fetal.
