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褪黑素通过调节转化生长因子-β通路促进间充质干细胞对2型糖尿病的治疗作用。

Melatonin Promotes the Therapeutic Effect of Mesenchymal Stem Cells on Type 2 Diabetes Mellitus by Regulating TGF-β Pathway.

作者信息

Li Balun, Cheng Xuedi, Aierken Aili, Du Jiaxin, He Wenlai, Zhang Mengfei, Tan Ning, Kou Zheng, Peng Sha, Jia Wenwen, Tang Haiyang, Hua Jinlian

机构信息

Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China.

Department of Animal Engineering, Yangling Vocational and Technical College, Xianyang, China.

出版信息

Front Cell Dev Biol. 2021 Oct 15;9:722365. doi: 10.3389/fcell.2021.722365. eCollection 2021.

DOI:10.3389/fcell.2021.722365
PMID:34722505
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8554153/
Abstract

Abundant evidence proves the therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) in the treatment of diabetes mellitus. However, the problems have not been solved that viability of ADMSCs were inconsistent and the cells quickly undergo senescence after cell culture. In addition, the therapeutic effect of ADMSCs is still not satisfactory. In this study, melatonin (MLT) was added to canine ADMSC culture medium, and the treated cells were used to treat type 2 diabetes mellitus (T2DM). Our research reveals that adding MLT to ADMSC culture medium can promote the viability of ADMSCs. This effect depends on the binding of MLT and MLT receptors, which activates the transforming growth factor β (TGF-β) pathway and then changes the cell cycle of ADMSCs and improves the viability of ADMSCs. Since ADMSCs were found to be used to treat T2DM by anti-inflammatory and anti-endoplasmic reticulum (ER) stress capabilities, our data demonstrate that MLT augment several effects of ADMSCs in remission hyperglycemia, insulin resistance, and liver glycogen metabolism in T2DM patients. This suggest that ADMSCs and MLT-ADMSCs is safe and vabulable for pet clinic.

摘要

大量证据证明脂肪间充质干细胞（ADMSCs）在治疗糖尿病方面具有治疗效果。然而，ADMSCs的活力不一致以及细胞在培养后迅速衰老的问题尚未得到解决。此外，ADMSCs的治疗效果仍不尽人意。在本研究中，将褪黑素（MLT）添加到犬ADMSC培养基中，并使用处理后的细胞治疗2型糖尿病（T2DM）。我们的研究表明，向ADMSC培养基中添加MLT可以提高ADMSCs的活力。这种作用取决于MLT与MLT受体的结合，其激活转化生长因子β（TGF-β）途径，进而改变ADMSCs的细胞周期并提高ADMSCs的活力。由于发现ADMSCs通过抗炎和抗内质网（ER）应激能力用于治疗T2DM，我们的数据表明，MLT增强了ADMSCs在缓解T2DM患者高血糖、胰岛素抵抗和肝糖原代谢方面的多种作用。这表明ADMSCs和MLT-ADMSCs对宠物临床是安全且有价值的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68af/8554153/6f47bfb51bb6/fcell-09-722365-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68af/8554153/9281b7319fa3/fcell-09-722365-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68af/8554153/a23601274c85/fcell-09-722365-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68af/8554153/de2a7e2c8890/fcell-09-722365-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68af/8554153/9281b7319fa3/fcell-09-722365-g005.jpg
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FASEB J. 2021 Jun;35(6):e21664. doi: 10.1096/fj.202100230R.
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inhibits family phosphatases and activates MAPK signaling pathway to maintain pluripotency in porcine induced pluripotent stem cells.抑制家族磷酸酶并激活 MAPK 信号通路，以维持猪诱导多能干细胞的多能性。
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Reversion of early- and late-stage β-cell dedifferentiation by human umbilical cord-derived mesenchymal stem cells in type 2 diabetic mice.
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SPARC overexpression in allogeneic adipose-derived mesenchymal stem cells in dog dry eye model induced by benzalkonium chloride.SPARC 在苯扎氯铵诱导的犬干眼模型中同种异体脂肪来源间充质干细胞中的过表达。
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