Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells

Sherwood Dalton, Kathryn Smith, Kanwar Singh, Helen Kaiser, Ravindra Kolhe, Ashis K. Mondal, Andrew Khayrullin, Carlos M. Isales, Mark W. Hamrick, William D. Hill, Sadanand Fulzele

Research output: Contribution to journalArticle

Abstract

Kynurenine, a metabolite of tryptophan breakdown, has been shown to increase with age, and plays a vital role in a number of age-related pathophysiological changes, including bone loss. Accumulation of kynurenine in bone marrow stromal cells (BMSCs) has been associated with a decrease in cell proliferation and differentiation, though the exact mechanism by which kynurenine mediates these changes is poorly understood. MiRNAs have been shown to regulate BMSC function, and accumulation of kynurenine may alter the miRNA expression profile of BMSCs. The aim of this study was to identify differentially expressed miRNAs in human BMSCs in response to treatment with kynurenine, and correlate miRNAs function in BMSCs biology through bioinformatics analysis. Human BMSCs were cultured and treated with and without kynurenine, and subsequent miRNA isolation was performed. MiRNA array was performed to identify differentially expressed miRNA. Microarray analysis identified 50 up-regulated, and 36 down-regulated miRNAs in kynurenine-treated BMSC cultures. Differentially expressed miRNA included miR-1281, miR-330-3p, let-7f-5p, and miR-493-5p, which are important for BMSC proliferation and differentiation. KEGG analysis found up-regulated miRNA targeting glutathione metabolism, a pathway critical for removing oxidative species. Our data support that the kynurenine dependent degenerative effect is partially due to changes in the miRNA profile of BMSCs.

Original languageEnglish (US)
Article number110800
JournalExperimental Gerontology
Volume130
DOIs
StatePublished - Feb 2020

Fingerprint

Kynurenine
Oxidative stress
MicroRNAs
Mesenchymal Stromal Cells
Bone
Oxidative Stress
Cell proliferation
Cell Differentiation
Cell Proliferation
Cells
Cytology
Critical Pathways
Microarray Analysis
Computational Biology
Tryptophan
Bioinformatics
Microarrays
Metabolites
Glutathione
Cell culture

Keywords

  • Human bone marrow stromal cells
  • Kynurenine
  • microRNAs
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells. / Dalton, Sherwood; Smith, Kathryn; Singh, Kanwar; Kaiser, Helen; Kolhe, Ravindra; Mondal, Ashis K.; Khayrullin, Andrew; Isales, Carlos M.; Hamrick, Mark W.; Hill, William D.; Fulzele, Sadanand.

In: Experimental Gerontology, Vol. 130, 110800, 02.2020.

Research output: Contribution to journalArticle

Dalton, S, Smith, K, Singh, K, Kaiser, H, Kolhe, R, Mondal, AK, Khayrullin, A, Isales, CM, Hamrick, MW, Hill, WD & Fulzele, S 2020, 'Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells', Experimental Gerontology, vol. 130, 110800. https://doi.org/10.1016/j.exger.2019.110800
Dalton, Sherwood ; Smith, Kathryn ; Singh, Kanwar ; Kaiser, Helen ; Kolhe, Ravindra ; Mondal, Ashis K. ; Khayrullin, Andrew ; Isales, Carlos M. ; Hamrick, Mark W. ; Hill, William D. ; Fulzele, Sadanand. / Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells. In: Experimental Gerontology. 2020 ; Vol. 130.
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