Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway
Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marr...
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oai:doaj.org-article:9154dfe513324bab97a9468703a40f052021-11-11T16:49:58ZCurcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway10.3390/ijms2221113561422-00671661-6596https://doaj.org/article/9154dfe513324bab97a9468703a40f052021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11356https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 μM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-β-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (<i>TNF-α</i>) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 μM~10 μM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene<i> (</i>Atg)<i> 7</i> and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs.Jiaqiang DengPing OuyangWeiyao LiLijun ZhongCongwei GuLiuhong ShenSuizhong CaoLizi YinZhihua RenZhicai ZuoJunliang DengQigui YanShumin YuMDPI AGarticlecurcuminsenescenceautophagycanine bone marrow-derived mesenchymal stem cellsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11356, p 11356 (2021) |
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curcumin senescence autophagy canine bone marrow-derived mesenchymal stem cells Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
curcumin senescence autophagy canine bone marrow-derived mesenchymal stem cells Biology (General) QH301-705.5 Chemistry QD1-999 Jiaqiang Deng Ping Ouyang Weiyao Li Lijun Zhong Congwei Gu Liuhong Shen Suizhong Cao Lizi Yin Zhihua Ren Zhicai Zuo Junliang Deng Qigui Yan Shumin Yu Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway |
| description |
Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 μM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-β-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (<i>TNF-α</i>) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 μM~10 μM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene<i> (</i>Atg)<i> 7</i> and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs. |
| format |
article |
| author |
Jiaqiang Deng Ping Ouyang Weiyao Li Lijun Zhong Congwei Gu Liuhong Shen Suizhong Cao Lizi Yin Zhihua Ren Zhicai Zuo Junliang Deng Qigui Yan Shumin Yu |
| author_facet |
Jiaqiang Deng Ping Ouyang Weiyao Li Lijun Zhong Congwei Gu Liuhong Shen Suizhong Cao Lizi Yin Zhihua Ren Zhicai Zuo Junliang Deng Qigui Yan Shumin Yu |
| author_sort |
Jiaqiang Deng |
| title |
Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway |
| title_short |
Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway |
| title_full |
Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway |
| title_fullStr |
Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway |
| title_full_unstemmed |
Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway |
| title_sort |
curcumin alleviates the senescence of canine bone marrow mesenchymal stem cells during in vitro expansion by activating the autophagy pathway |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/9154dfe513324bab97a9468703a40f05 |
| work_keys_str_mv |
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| _version_ |
1718432252925313024 |