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

被引：14
作者：
Li, Balun [1 ]
Cheng, Xuedi [1 ]
Aierken, Aili [1 ]
Du, Jiaxin [2 ,3 ]
He, Wenlai [1 ]
Zhang, Mengfei [1 ]
Tan, Ning [1 ]
Kou, Zheng [1 ]
Peng, Sha [1 ]
Jia, Wenwen [4 ]
Tang, Haiyang [1 ,5 ]
Hua, Jinlian [1 ]
机构：
[1] Northwest A&F Univ, Coll Vet Med, Shaanxi Ctr Stem Cells Engn & Technol, Xianyang, Peoples R China
[2] Yangling Vocat & Tech Coll, Dept Anim Engn, Xianyang, Peoples R China
[3] Zhejiang Univ, Coll Anim Sci, Inst Prevent Vet Sci, Dept Vet Med, Hangzhou, Peoples R China
[4] Tongji Univ, East Hosp, Shanghai East Hosp, Shanghai, Peoples R China
[5] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Hlth, State Key Lab Resp Dis, Guangzhou, Peoples R China
来源：
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 9卷
基金：
中国国家自然科学基金;
关键词：
melatonin; adipose-derived mesenchymal stem cells; type 2 diabetes mellitus; TGF-beta; inflammation; canine; GROWTH-FACTOR-BETA; SIGNALING PATHWAY; STRESS; APOPTOSIS; HYPERGLYCEMIA; DIFFERENTIATION; INFLAMMATION; METABOLISM; MECHANISMS; MATURATION;
D O I：
10.3389/fcell.2021.722365
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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 in vitro 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 beta (TGF-beta) 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.
引用
收藏
页数：20
相关论文
共 70 条
[21]   Melatonin plays critical role in mesenchymal stem cell-based regenerative medicine in vitro and in vivo [J].
Hu, Chenxia ;
Li, Lanjuan .
STEM CELL RESEARCH & THERAPY, 2019, 10 (1)
[22]   Sodium butyrate mitigates type 2 diabetes by inhibiting PERK-CHOP pathway of endoplasmic reticulum stress [J].
Hu Yimeng ;
Liu Jie ;
Yuan Yin ;
Chen Jing ;
Cheng Siyuan ;
Wang Huawei ;
Xu Yancheng .
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, 2018, 64 :112-121
[23]   Cytoprotective effects of melatonin on zoledronic acid-treated human mesenchymal stem cells in vitro [J].
Javier Rodriguez-Lozano, Francisco ;
Garcia-Bernal, David ;
de los Angeles Ros-Roca, Maria ;
del Carmen Alguero, Maria ;
Elias Onate-Sanchez, Ricardo ;
Camacho-Alonso, Fabio ;
Maria Moraleda, Jose .
JOURNAL OF CRANIO-MAXILLOFACIAL SURGERY, 2015, 43 (06) :855-862
[24]   Accumulation of apoptosis-insensitive human bone marrow-mesenchymal stromal cells after long-term expansion [J].
Jeong, Sin-Gu ;
Cho, Goang-Won .
CELL BIOCHEMISTRY AND FUNCTION, 2016, 34 (05) :310-316
[25]   Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals [J].
Jha, Pawan Kumar ;
Challet, Etienne ;
Kalsbeek, Andries .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2015, 418 :74-88
[26]   Melatonin improves the therapeutic role of mesenchymal stem cells in diabetic rats [J].
Kadry, Shadia M. ;
El-Dakdoky, Mai H. ;
Haggag, Nawal Z. ;
Rashed, Laila A. ;
Hassen, Marwa T. .
TOXICOLOGY MECHANISMS AND METHODS, 2018, 28 (07) :529-538
[27]   Melatonin prevents cadmium-induced bone damage: First evidence on an improved osteogenic/adipogenic differentiation balance of mesenchymal stem cells as underlying mechanism [J].
Knani, Latifa ;
Bartolini, Desiree ;
Kechiche, Safa ;
Tortoioli, Cristina ;
Murdolo, Giuseppe ;
Moretti, Massimo ;
Messaoudi, Imed ;
Reiter, Russel J. ;
Galli, Francesco .
JOURNAL OF PINEAL RESEARCH, 2019, 67 (03)
[28]   Melatonin enhances the human mesenchymal stem cells motility via melatonin receptor 2 coupling with Gαq in skin wound healing [J].
Lee, Sei-Jung ;
Jung, Young Hyun ;
Oh, Sang Yub ;
Yun, Seung Pil ;
Han, Ho Jae .
JOURNAL OF PINEAL RESEARCH, 2014, 57 (04) :393-407
[29]   Reversion of early- and late-stage β-cell dedifferentiation by human umbilical cord-derived mesenchymal stem cells in type 2 diabetic mice [J].
Li, Bing ;
Cheng, Yu ;
Yin, Yaqi ;
Xue, Jing ;
Yu, Songyan ;
Gao, Jieqing ;
Liu, Jiejie ;
Zang, Li ;
Mu, Yiming .
CYTOTHERAPY, 2021, 23 (06) :510-520
[30]   Transforming growth factor-β regulation of immune responses [J].
Li, Ming O. ;
Wan, Yisong Y. ;
Sanjabi, Shomyseh ;
Robertson, Anna-Karin L. ;
Flavell, Richard A. .
ANNUAL REVIEW OF IMMUNOLOGY, 2006, 24 :99-146
1234567