Indoleamine 2, 3-dioxygenase (IDO) increases during renal fibrogenesis and its inhibition potentiates TGF-β 1-induced epithelial to mesenchymal transition

BMC Nephrology

Research Article

Alexandre Chagas Santana¹  Taíssa Altieri Amaral¹  Camila Soares Malta¹  Rodrigo Barbosa Oliveira Brito¹  Luiz Henrique Gomes Matheus¹  Gislene Mendes Simão¹  Maria Clara Albejante¹  Maria Aparecida Dalboni¹  Erna Elisabeth Bach¹  Humberto Dellê¹  Gabriela Gomes Cardoso Rodrigues¹  Cleber Pinto Camacho¹  Yves Silva Teles Matos¹ 

[1] Postgraduate Program in Medicine, Universidade Nove de Julho (UNINOVE), Rua Vergueiro, 235, 2º subsolo, 01504-001, São Paulo, São Paulo, Brazil;

关键词: Indoleamine 2, 3-dioxygenase;    1-methyl-D-tryptophan;    Renal fibrosis;    Epithelial to mesenchymal transition;    TGF-β 1;    Renal inflammation;   

DOI  :  10.1186/s12882-017-0702-7

 received in 2016-08-02, accepted in 2017-08-22,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundIndoleamine 2, 3-dioxygenase (IDO) is an immunomodulatory molecule that has been implicated in several biological processes. Although IDO has been linked with some renal diseases, its role in renal fibrosis is still unclear. Because IDO may be modulated by TGF-β1, a potent fibrogenic molecule, we hypothesized that IDO could be involved in renal fibrosis, especially acting in the TGF-β1-induced tubular epithelial-mesenchymal transition (EMT). We analyzed the IDO expression and activity in a model of renal fibrogenesis, and the effect of the IDO inhibitor 1-methyl-tryptophan (MT) on TGF-β1-induced EMT using tubular cell culture.MethodsMale Wistar rats where submited to 7 days of UUO. Non-obstructed kidneys (CL) and kidneys from SHAM rats were used as controls. Masson’s Tricrome and macrophages counting were used to chatacterize the tissue fibrosis. The EMT was analysed though immunohistochemistry and qRT-PCR. Immunohistochemestry in tissue has used to show IDO expression.MDCK cells were incubated with TGF- β1 to analyse IDO expression. Additionally, effects of TGF- β1 and the inhibition of IDO over the EMT process was acessed by immunoessays and scrath wound essay.ResultsIDO was markedly expressed in cortical and medular tubules of the UUO kidneys. Similarly to the immunolocalizaton of TGF- β1, accompanied by loss of e-cadherin expression and an increase of mesenchymal markers. Results in vitro with MDCK cells, showed that IDO was increased after stimulus with TGF-β1, and treatment with MT potentiated its expression. MDCK stimulated with TGF-β1 had higher migratory activity (scratch-wound assay), which was exacerbated by MT treatment.ConclusionsIDO is constitutively expressed in tubular cells and increases during renal fibrogenesis. Although IDO is induced by TGF-β1 in tubular cells, its chemical inhibitor acts as a profibrotic agent.

【 授权许可】

CC BY   
© The Author(s). 2017