PMID- 30657854
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20190624
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 60
IP  - 1
DP  - 2019 Jan 2
TI  - Exosomes Derived From Mesenchymal Stem Cells Modulate miR-126 to Ameliorate 
      Hyperglycemia-Induced Retinal Inflammation Via Targeting HMGB1.
PG  - 294-303
LID - 10.1167/iovs.18-25617 [doi]
AB  - PURPOSE: In this study, we aim to investigate whether mesenchymal stem cell 
      (MSC)-derived exosomes (MSC-Exos) could regulate hyperglycemia-induced retinal 
      inflammation by transferring microRNA-126 (miR-126). METHODS: MSC-Exos were 
      isolated from the media of human umbilical cord-derived mesenchymal stem cells 
      (hUCMSCs), and this isolation was followed by the transfer of miR-126. MSC-Exos 
      or MSC-Exos overexpressing miR-126 were intravitreally injected into diabetic 
      rats in vivo and were cocultured with high glucose-affected human retinal 
      endothelial cells (HRECs) in vitro. Plasma samples were obtained from the 
      vitreous of rats and from HREC cells after treatment for ELISA assay. Retinal 
      sections were examined using immunohistochemistry. RT-PCR and Western blotting 
      were conducted to assess the levels of high-mobility group box 1 (HMGB1), NLRP3 
      inflammasome, and NF-kappaB/P65 in retinas and HRECs. RESULTS: Our results showed 
      that hyperglycemia greatly increased inflammation in diabetic rats or HRECs 
      exposed to high glucose, increasing the levels of caspase-1, interleukin-1beta 
      (IL-1beta) and IL-18. The administration of MSC-Exos could effectively reverse this 
      reaction. Compared to control MSC-Exos, MSC-Exos overexpressing miR-126 more 
      successfully suppressed the HMGB1 signaling pathway and suppressed inflammation 
      in diabetic rats. The administration of miR-126-expressing MSC-Exos significantly 
      reduced high glucose-induced HMGB1 expression and the activity of the NLRP3 
      inflammasome in HRECs. CONCLUSIONS: miR-126 expression in MSC-Exos reduces 
      hyperglycemia-induced retinal inflammation by downregulating the HMGB1 signaling 
      pathway.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, 
      Tianjin Eye Institute, Clinical College of Ophthalmology, Tianjin Medical 
      University, Tianjin, China.
FAU - Wang, Yang
AU  - Wang Y
AD  - Department of Ophthalmology, Tianjin Medical University General Hospital, 
      Tianjin, China.
FAU - Kong, Yichun
AU  - Kong Y
AD  - Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, 
      Tianjin Eye Institute, Clinical College of Ophthalmology, Tianjin Medical 
      University, Tianjin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (HMGB1 Protein)
RN  - 0 (Hbp1 protein, rat)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (MIRN126 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Caspase 1/metabolism
MH  - Coculture Techniques
MH  - Diabetes Mellitus, Experimental/etiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Exosomes/*metabolism
MH  - HMGB1 Protein/*metabolism
MH  - Hyperglycemia/complications/metabolism/*prevention & control
MH  - Immunohistochemistry
MH  - Interleukin-18/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Mesenchymal Stem Cells/*metabolism
MH  - MicroRNAs/*metabolism
MH  - Rats
MH  - Real-Time Polymerase Chain Reaction
MH  - Retinitis/etiology/metabolism/*prevention & control
EDAT- 2019/01/19 06:00
MHDA- 2019/06/25 06:00
CRDT- 2019/01/19 06:00
PHST- 2019/01/19 06:00 [entrez]
PHST- 2019/01/19 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
AID - 2722918 [pii]
AID - 10.1167/iovs.18-25617 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2019 Jan 2;60(1):294-303. doi: 10.1167/iovs.18-25617.