PMID- 35902972
OWN - NLM
STAT- MEDLINE
DCOM- 20220801
LR  - 20220830
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Jul 28
TI  - Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates 
      the inflammation and tubular epithelial-myofibroblast transdifferentiation of 
      renal tubular epithelial cells by reducing ADAM19 protein levels.
PG  - 373
LID - 10.1186/s13287-022-03071-z [doi]
LID - 373
AB  - BACKGROUND: Renal tubular epithelial-myofibroblast transdifferentiation (EMT) 
      plays a key role in the regulation of renal fibrosis. Exosomes derived from human 
      umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in 
      alleviating renal fibrosis and injury. Additionally, hucMSC-derived exosomes 
      contain numerous microRNAs (miRNAs). However, it is unclear whether mesenchymal 
      stem cells can regulate the transforming growth factor (TGF)-beta1-induced EMT of 
      human renal tubular epithelial cells (RTECs) through exosomal miRNAs. METHOD: 
      HK-2, a human RTEC line, was co-treated with TGF-beta1 and hucMSC-derived exosomes. 
      Additionally, TGF-beta1-treated HK-2 cells were transfected with a miR-335-5p mimic 
      and disintegrin and metalloproteinase domain-containing protein 19 
      (ADAM19)-overexpression plasmid. miR-335-5p expression and ADAM19 protein and 
      inflammation levels were measured via quantitative reverse transcription 
      polymerase chain reaction, western blotting, and enzyme-linked immunosorbent 
      assays, respectively. RESULTS: TGF-beta1 treatment changed the shape of HK-2 cells 
      from a cobblestone morphology to a long spindle shape, accompanied by an increase 
      in interleukin (IL)-6, tumor necrosis factor-alpha, IL-1beta, collagen I, collagen III, 
      alpha-smooth muscle actin, vimentin, and N-cadherin protein levels, whereas 
      E-cadherin protein levels were reduced in these HK-2 cells, suggesting that 
      TGF-beta1 treatment induced the inflammation and EMT of HK-2 cells. HucMSC-exosomes 
      improved the inflammation and EMT phenotype of TGF-beta1-induced HK-2 cells by 
      transferring miR-335-5p. miR-335-5p was found to bind the ADAM19 3'-untranslated 
      region to reduce ADAM19 protein levels. Additionally, miR-335-5p improved the 
      inflammation and EMT phenotype of HK-2 cells by reducing ADAM19 protein levels 
      with TGF-beta1 induction. CONCLUSIONS: HucMSC-derived exosomal miR-335-5p attenuates 
      the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon 
      TGF-beta1 induction. This study provides a potential therapeutic strategy and 
      identifies targets for clinically treating renal fibrosis.
CI  - (c) 2022. The Author(s).
FAU - Qiu, Zhenhua
AU  - Qiu Z
AD  - Department of Laboratory Medicine, The People's Hospital of Gaozhou, Maoming, 
      525200, China. doctorqzh@163.com.
FAU - Zhong, Zhihui
AU  - Zhong Z
AD  - Department of Laboratory Medicine, The People's Hospital of Gaozhou, Maoming, 
      525200, China.
FAU - Zhang, Yuehan
AU  - Zhang Y
AD  - Department of Laboratory Medicine, The People's Hospital of Gaozhou, Maoming, 
      525200, China.
FAU - Tan, Haoling
AU  - Tan H
AD  - Department of Laboratory Medicine, The People's Hospital of Gaozhou, Maoming, 
      525200, China.
FAU - Deng, Bo
AU  - Deng B
AD  - Department of Laboratory Medicine, The People's Hospital of Gaozhou, Maoming, 
      525200, China.
FAU - Meng, Guohuang
AU  - Meng G
AD  - Department of Laboratory Medicine, The People's Hospital of Gaozhou, Maoming, 
      525200, China.
LA  - eng
PT  - Journal Article
DEP - 20220728
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (MIRN335 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (ADAM19 protein, human)
SB  - IM
MH  - ADAM Proteins/metabolism
MH  - Cell Transdifferentiation/genetics
MH  - Epithelial Cells/metabolism
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Fibrosis
MH  - Humans
MH  - Inflammation/genetics/metabolism/therapy
MH  - *Mesenchymal Stem Cells/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - Myofibroblasts/metabolism
MH  - Transforming Growth Factor beta1/metabolism
MH  - Umbilical Cord
PMC - PMC9330665
OTO - NOTNLM
OT  - Chronic kidney disease
OT  - Exosome
OT  - Renal fibrosis
OT  - miRNA
COIS- The authors declare that they have no competing interests.
EDAT- 2022/07/29 06:00
MHDA- 2022/08/02 06:00
PMCR- 2022/07/28
CRDT- 2022/07/28 23:53
PHST- 2022/05/17 00:00 [received]
PHST- 2022/07/20 00:00 [accepted]
PHST- 2022/07/28 23:53 [entrez]
PHST- 2022/07/29 06:00 [pubmed]
PHST- 2022/08/02 06:00 [medline]
PHST- 2022/07/28 00:00 [pmc-release]
AID - 10.1186/s13287-022-03071-z [pii]
AID - 3071 [pii]
AID - 10.1186/s13287-022-03071-z [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2022 Jul 28;13(1):373. doi: 10.1186/s13287-022-03071-z.