Proteomics study of the antifibrotic effects of α-mangostin in a rat model of renal fibrosis
Article Category: Original article
Published Online: Sep 25, 2019
Page range: 149 - 160
DOI: https://doi.org/10.1515/abm-2019-0015
Keywords
© 2018 Thana Chaeyklinthes et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.
Background
Renal fibrosis is a consequence of a “faulty” wound-healing mechanism that results in the accumulation of extracellular matrix, which could lead to the impairment of renal functions. α-Mangostin (AM) may prevent the formation of liver fibrosis, but there has yet to be a conclusive investigation of its effect on renal fibrosis.
Objectives
To investigate the renoprotective effect of AM against thioacetamide (TAA)-induced renal fibrosis in rats at the morphological and proteomic levels.
Methods
We divided 18 male Wistar rats into 3 groups: a control group, a TAA-treated group, and a TAA + AM group. The various agents used to treat the rats were administered intraperitoneally over 8 weeks. Subsequently, the morphology of renal tissue was analyzed by histology using Sirius Red staining and the relative amount of stained collagen fibers quantified using ImageJ analysis. One-dimensional gel liquid chromatography with tandem mass spectrometry (GeLC-MS/MS) was used to track levels of protein expression. Proteomic bioinformatics tools including STITCH were used to correlate the levels of markers known to be involved in fibrosis with Sirius Red-stained collagen scoring.
Results
Histology revealed that AM could reduce the relative amount of collagen fibers significantly compared with the TAA group. Proteomic analysis revealed the levels of 4 proteins were modulated by AM, namely CASP8 and FADD-like apoptosis regulator (Cflar), Ragulator complex protein LAMTOR3 (Lamtor3), mitogen-activated protein kinase kinase kinase 14 (Map3k14), and C-Jun-amino-terminal kinase-interacting protein 3 (Mapk8ip3).
Conclusion
AM can attenuate renal fibrosis by the suppression of pathways involving Cflar, Lamtor3, Map3k14, and Mapk8ip3.