PMID- 35434020
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 10
IP  - 6
DP  - 2022 Mar
TI  - MiR-146a upregulates FOXP3 and suppresses inflammation by targeting HIPK3/STAT3 
      in allergic conjunctivitis.
PG  - 344
LID - 10.21037/atm-22-982 [doi]
LID - 344
AB  - BACKGROUND: Allergic conjunctivitis (AC) is an inflammation caused by a 
      hypersensitive immune reaction of conjunctiva to external allergens. The microRNA 
      (miRNA) miR-146a has been reported to suppress the exacerbation of inflammation. 
      However, the underlying influence and mechanism of miR-146a in AC has not been 
      completely elucidated. METHODS: We first successfully established an AC mouse 
      model and AC cell model. After each model was treated based on the experimental 
      purposes, miR-146a, FOXP3, and homeodomain-interacting protein kinases 3 (HIPK3) 
      expressions were estimated by reverse transcription quantitative polymerase chain 
      reaction (RT-qPCR). The levels of immunoglobulin E (IgE), tumor necrosis factor-alpha 
      (TNF-alpha), interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth 
      factor-beta (TGF-beta) were assessed using enzyme-linked immunosorbent assay (ELISA) 
      kits; the related proteins were analyzed by western blot, immunofluorescence, or 
      immunohistochemistry (IHC) assays; the interaction between miR-146a and HIPK3 
      were validated by a dual-luciferase reporter gene assay; and the inflammatory 
      infiltration was certified by hematoxylin and eosin (H&E) staining. RESULTS: Our 
      results indicated that miR-146a and FOXP3 were downregulated in AC model mice. 
      Meanwhile, miR-146a overexpression could upregulate FOXP3 and inhibit 
      inflammatory response in TGF-beta-induced thymocytes. Besides, our results testified 
      that HIPK3, as a target gene of miR-146a, could reverse miR-146a-mediated FOXP3 
      upregulation and inflammation inhibition. Moreover, we discovered that miR-146a 
      could downregulate p-STAT3 by targeting HIPK3, and activation of STAT3 also could 
      reverse miR-146a-mediated inflammation suppression in TGF-beta-induced thymocytes. 
      More importantly, miR-146a could ameliorate inflammatory infiltration and 
      downregulate HIPK3 and p-STAT3 in AC model mice. CONCLUSIONS: We demonstrated a 
      possible protective mechanism by the miR-146a/HIPK3/STAT3 axis, by which decrease 
      of miR-146a could aggravate the inflammation of AC.
CI  - 2022 Annals of Translational Medicine. All rights reserved.
FAU - Guo, Hui
AU  - Guo H
AD  - Shenzhen Eye Hospital, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated 
      to Jinan University, Shenzhen, China.
FAU - Zhang, Yongxin
AU  - Zhang Y
AD  - School of Optometry, Shenzhen University, Shenzhen, China.
FAU - Liao, Zifang
AU  - Liao Z
AD  - Shenzhen Eye Hospital, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated 
      to Jinan University, Shenzhen, China.
FAU - Zhan, Wenzhu
AU  - Zhan W
AD  - Shenzhen Eye Hospital, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated 
      to Jinan University, Shenzhen, China.
FAU - Wang, Yuan
AU  - Wang Y
AD  - Shenzhen Eye Hospital, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated 
      to Jinan University, Shenzhen, China.
FAU - Peng, Yun
AU  - Peng Y
AD  - Shenzhen Eye Hospital, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated 
      to Jinan University, Shenzhen, China.
FAU - Yang, Meina
AU  - Yang M
AD  - Shenzhen Eye Hospital, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated 
      to Jinan University, Shenzhen, China.
FAU - Ma, Xudai
AU  - Ma X
AD  - Shenzhen Eye Hospital, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated 
      to Jinan University, Shenzhen, China.
FAU - Yin, Guogan
AU  - Yin G
AD  - Shenzhen Eye Hospital, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated 
      to Jinan University, Shenzhen, China.
FAU - Ye, Lin
AU  - Ye L
AD  - Shenzhen Eye Hospital, Shenzhen Eye Institute, Shenzhen Eye Hospital Affiliated 
      to Jinan University, Shenzhen, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC9011242
OTO - NOTNLM
OT  - FOXP3
OT  - STAT3
OT  - allergic conjunctivitis (AC)
OT  - homeodomain-interacting protein kinases 3 (HIPK3)
OT  - inflammation
OT  - miR-146a
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://atm.amegroups.com/article/view/10.21037/atm-22-982/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2022/04/19 06:00
MHDA- 2022/04/19 06:01
PMCR- 2022/03/01
CRDT- 2022/04/18 06:40
PHST- 2022/01/20 00:00 [received]
PHST- 2022/03/21 00:00 [accepted]
PHST- 2022/04/18 06:40 [entrez]
PHST- 2022/04/19 06:00 [pubmed]
PHST- 2022/04/19 06:01 [medline]
PHST- 2022/03/01 00:00 [pmc-release]
AID - atm-10-06-344 [pii]
AID - 10.21037/atm-22-982 [doi]
PST - ppublish
SO  - Ann Transl Med. 2022 Mar;10(6):344. doi: 10.21037/atm-22-982.