TY - JOUR
T1 - Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells
AU - Dalton, Sherwood
AU - Smith, Kathryn
AU - Singh, Kanwar
AU - Kaiser, Helen
AU - Kolhe, Ravindra
AU - Mondal, Ashis K.
AU - Khayrullin, Andrew
AU - Isales, Carlos M.
AU - Hamrick, Mark W.
AU - Hill, William D.
AU - Fulzele, Sadanand
N1 - Published by Elsevier Inc.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Human bone marrow stromal cells
KW - Kynurenine
KW - Oxidative stress
KW - microRNAs
UR - http://www.scopus.com/inward/record.url?scp=85076034093&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076034093&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2019.110800
DO - 10.1016/j.exger.2019.110800
M3 - Article
C2 - 31790802
AN - SCOPUS:85076034093
SN - 0531-5565
VL - 130
SP - 110800
JO - Experimental Gerontology
JF - Experimental Gerontology
M1 - 110800
ER -