Integration of transcriptomics and metabolomics reveals pathways involved in MDSC supernatant attenuation of TGF-β1-induced myofibroblastic differentiation of mesenchymal stem cells.

Autor: Cheuk YC; Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Niu X; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Mao Y; Department of Urology, Huadong Hospital, Fudan University, Shanghai, 200040, China., Li J; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Wang J; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Xu S; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.; Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China., Luo Y; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Wang W; Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Wang X; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China. wang.xuanchuan@zs-hospital.sh.cn.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. wang.xuanchuan@zs-hospital.sh.cn., Zhang Y; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China. yzhang_med@fudan.edu.cn.; Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. yzhang_med@fudan.edu.cn., Rong R; Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China. rong.ruiming@zs-hospital.sh.cn.; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. rong.ruiming@zs-hospital.sh.cn.
Jazyk: angličtina
Zdroj: Cell and tissue research [Cell Tissue Res] 2022 Dec; Vol. 390 (3), pp. 465-489. Date of Electronic Publication: 2022 Sep 13.
DOI: 10.1007/s00441-022-03681-2
Abstrakt: Overexposure to transforming growth factor b1 (TGF-β1) induces myofibroblastic differentiation of mesenchymal stem cells (MSCs), which could be attenuated by myeloid-derived suppressor cell (MDSC) supernatant. However, the promyofibroblastic effects of TGF-β1 and the antimyofibroblastic effects of MDSC supernatant in MSCs have not been fully elucidated. To further clarify the latent mechanism and identify underlying therapeutic targets, we used an integrative strategy combining transcriptomics and metabolomics. Bone marrow MSCs were collected 24 h following TGF-β1 and MDSC supernatant treatment for RNA sequencing and untargeted metabolomic analysis. The integrated data were then analyzed to identify significant gene-metabolite correlations. Differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) were assessed by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for exploring the mechanisms of myofibroblastic differentiation of MSCs. The integration of transcriptomic and metabolomic data highlighted significantly coordinated changes in glycolysis/gluconeogenesis and purine metabolism following TGF-β1 and MDSC supernatant treatment. By combining transcriptomic and metabolomic analyses, this study showed that glycolysis/gluconeogenesis and purine metabolism were essential for the myofibroblastic differentiation of MSCs and may serve as promising targets for mechanistic research and clinical practice in the treatment of fibrosis by MDSC supernatant.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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