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Clin Exp Nephrol ; 22(4): 906-916, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29453607

RESUMO

BACKGROUND: Semaphorin 7A (SEMA7A) is an immunomodulating protein implicated in lung and liver fibrosis. In autosomal-dominant polycystic kidney disease (ADPKD), the progressive expansion of renal cysts, inflammation, and subsequent renal fibrosis leads to end-stage renal disease (ESRD). SEMA7A may play a role in renal fibrosis and in ADPKD. METHODS: We evaluated Sema7a in a mouse model of renal fibrosis and determined the expression of SEMA7A in human ADPKD kidney. We analyzed SEMA7A expression on peripheral blood mononuclear cells (PBMCs), including CD45+ (leukocyte), CD14+(monocyte), CD4+ (T lymphocytes) and CD4+Foxp3+CD25+ [regulatory T lymphocytes (Tregs)] from 90 ADPKD patients (11 tolvaptan treated and 79 tolvaptan naïve), and 21 healthy volunteers, using a Fluorescence-Activated Cell Sorting (FACS). RESULTS: Sema7a is required for renal fibrosis. SEMA7A shows robust expression in ADPKD kidneys, localizing to cysts derived from distal tubules. SEMA7A is higher in circulating monocytes, but unchanged in CD4+ lymphocytes in ADPKD patients. The SEMA7A increase was detected early (stage 1 CKD) and seemed more prominent in patients with smaller kidneys (p = 0.09). Compared to tolvaptan-naïve ADPKD patients, those treated with tolvaptan showed reduced SEMA7A expression on monocytes, T lymphocytes, and Tregs, although the number of PBMCs was unchanged. After 1 month of tolvaptan treatment, SEMA7A expression on Tregs decreased. CONCLUSIONS: SEMA7A shows potential as both a therapeutic target in mammalian kidney fibrosis and as a marker of inflammation in ADPKD patients. SEMA7A expression was lower after tolvaptan treatment, which may reflect drug efficacy.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Antígenos CD/análise , Rim Policístico Autossômico Dominante/tratamento farmacológico , Semaforinas/análise , Linfócitos T Reguladores , Tolvaptan/uso terapêutico , Animais , Feminino , Proteínas Ligadas por GPI/análise , Humanos , Rim , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/imunologia
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