PMID- 37248536
OWN - NLM
STAT- MEDLINE
DCOM- 20230531
LR  - 20230603
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 14
IP  - 1
DP  - 2023 May 29
TI  - Intravenous injection of human umbilical cord-derived mesenchymal stem cells 
      ameliorates not only blood glucose but also nephrotic complication of diabetic 
      rats through autophagy-mediated anti-senescent mechanism.
PG  - 146
LID - 10.1186/s13287-023-03354-z [doi]
LID - 146
AB  - BACKGROUND: Diabetic nephropathy (DN) is one of the most severe complications of 
      diabetes mellitus, which is characterized by early occurrence of albuminuria and 
      end-stage glomerulosclerosis. Senescence and autophagy of podocytes play an 
      important role in DN development. Human umbilical cord-derived mesenchymal stem 
      cells (hucMSCs) have potential in the treatment of diabetes and its 
      complications. However, the role of hucMSCs in the treatment of DN and the 
      underlying mechanism remain unclear. METHODS: In vivo, a streptozotocin-induced 
      diabetic male Sprague Dawley rat model was established to determine the 
      renoprotective effect of hucMSCs on DN by biochemical analysis, histopathology, 
      and immunohistochemical staining of renal tissues. And the distribution of 
      hucMSCs in various organs in rats within 168 h was analyzed. In vitro, CCK8 
      assay, wound healing assay, and beta-galactosidase staining were conducted to detect 
      the beneficial effects of hucMSCs on high glucose-induced rat podocytes. 
      Real-time PCR and western blot assays were applied to explore the mechanism of 
      action of hucMSCs. RESULTS: The in vivo data revealed that hucMSCs were 
      distributed into kidneys and significantly protected kidneys from diabetic 
      damage. The in vitro data indicated that hucMSCs improved cell viability, wound 
      healing, senescence of the high glucose-damaged rat podocytes through a paracrine 
      action mode. Besides, the altered expressions of senescence-associated genes 
      (p16, p53, and p21) and autophagy-associated genes (Beclin-1, p62, and LC3) were 
      improved by hucMSCs. Mechanistically, hucMSCs protected high glucose-induced 
      injury in rat podocytes by activating autophagy and attenuating senescence 
      through the AMPK/mTOR pathway. CONCLUSIONS: In conclusion, hucMSCs might be a 
      promising therapeutic strategy for the clinical treatment of DN-induced renal 
      damages.
CI  - (c) 2023. The Author(s).
FAU - Li, Xinyue
AU  - Li X
AD  - School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 
      China.
FAU - Guo, Le
AU  - Guo L
AD  - School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 
      China.
FAU - Chen, Jingan
AU  - Chen J
AD  - School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 
      China.
FAU - Liang, Haowei
AU  - Liang H
AD  - School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 
      China.
FAU - Liu, Yi
AU  - Liu Y
AD  - School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 
      China.
FAU - Chen, Wei
AU  - Chen W
AD  - Cancer Institute of Integrated Traditional Chinese and Western Medicine, Key 
      Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and 
      Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese 
      Medicine, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, 310012, 
      Zhejiang, China.
FAU - Zhou, Li
AU  - Zhou L
AD  - The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 
      China. zhouli@zcmu.edu.cn.
FAU - Shan, Letian
AU  - Shan L
AD  - The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 
      China. letian.shan@zcmu.edu.cn.
AD  - Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, 
      Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd), 
      Hangzhou, China. letian.shan@zcmu.edu.cn.
FAU - Wang, Hui
AU  - Wang H
AUID- ORCID: 0000-0003-0108-8254
AD  - School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 
      China. wh@zcmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230529
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Blood Glucose)
SB  - IM
MH  - Rats
MH  - Humans
MH  - Male
MH  - Animals
MH  - Rats, Sprague-Dawley
MH  - Blood Glucose/metabolism
MH  - *Diabetes Mellitus, Experimental/metabolism
MH  - Injections, Intravenous
MH  - *Diabetic Nephropathies/therapy/metabolism
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Autophagy
MH  - Umbilical Cord/metabolism
PMC - PMC10228071
OTO - NOTNLM
OT  - AMPK/mTOR signaling
OT  - Diabetic nephropathy
OT  - Human umbilical cord-derived mesenchymal stem cells
OT  - Paracrine effect
OT  - Podocytes
COIS- The authors declare no competing interests.
EDAT- 2023/05/30 01:06
MHDA- 2023/05/31 06:42
PMCR- 2023/05/29
CRDT- 2023/05/29 23:34
PHST- 2022/07/20 00:00 [received]
PHST- 2023/04/24 00:00 [accepted]
PHST- 2023/05/31 06:42 [medline]
PHST- 2023/05/30 01:06 [pubmed]
PHST- 2023/05/29 23:34 [entrez]
PHST- 2023/05/29 00:00 [pmc-release]
AID - 10.1186/s13287-023-03354-z [pii]
AID - 3354 [pii]
AID - 10.1186/s13287-023-03354-z [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2023 May 29;14(1):146. doi: 10.1186/s13287-023-03354-z.