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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Gomes Matheus, Luiz Henrique ; Simao, Gislene Mendes ; Amaral, Taissa Altieri ; Oliveira Brito, Rodrigo Barbosa ; Malta, Camila Soares ; Teles Matos, Yves Silva ; Santana, Alexandre Chagas ; Cardoso Rodrigues, Gabriela Gomes ; Albejante, Maria Clara ; Bach, Erna Elisabeth ; Dalboni, Maria Aparecida ; Camacho, Cleber Pinto ; Delle, Humberto
Total Authors: 13
Document type: Journal article
Source: BMC Nephrology; v. 18, SEP 6 2017.
Web of Science Citations: 1

Background: Indoleamine 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-beta 1, a potent fibrogenic molecule, we hypothesized that IDO could be involved in renal fibrosis, especially acting in the TGF-beta 1-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-beta 1-induced EMT using tubular cell culture. Methods: Male 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 characterize 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-beta 1 to analyse IDO expression. Additionally, effects of TGF-beta 1 and the inhibition of IDO over the EMT process was acessed by immunoessays and scrath wound essay. Results: IDO was markedly expressed in cortical and medular tubules of the UUO kidneys. Similarly to the immunolocalizaton of TGF-beta 1, 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-beta 1, and treatment with MT potentiated its expression. MDCK stimulated with TGF-beta 1 had higher migratory activity (scratch-wound assay), which was exacerbated by MT treatment. Conclusions: IDO is constitutively expressed in tubular cells and increases during renal fibrogenesis. Although IDO is induced by TGF-beta 1 in tubular cells, its chemical inhibitor acts as a profibrotic agent. (AU)

FAPESP's process: 13/07183-3 - Analysis of the indoleamine 2,3 - dioxygenase (IDO) expression in renal tissue during the epithelial-mesenchymal transition process induced in the model of ureteral unilateral obstruction (UUO)
Grantee:Gislene Mendes Simão
Support type: Scholarships in Brazil - Scientific Initiation