PMID- 34605097
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20220531
IS  - 1469-445X (Electronic)
IS  - 0958-0670 (Linking)
VI  - 106
IP  - 12
DP  - 2021 Dec
TI  - miR-302a-3p targets FMR1 to regulate pyroptosis of renal tubular epithelial cells 
      induced by hypoxia-reoxygenation injury.
PG  - 2531-2541
LID - 10.1113/EP089887 [doi]
AB  - NEW FINDINGS: What is the central question of this study? How does miR-302a-3p 
      play a role in hypoxia-reoxygenation-induced pyroptosis of renal tubular 
      epithelial cells? What is the main finding and its importance? 
      Hypoxia-reoxygenation treatment upregulated the expression of miR-302a-3p in HK-2 
      cells, and then inhibited the transcription of FMRP translational regulator 1 
      (FMR1), so as to promote the activation of the NLRP3 inflammasome and aggravate 
      the pyroptosis of HK-2 cells. miR-302a-3p was used as a molecular target in this 
      study, which provides a new theoretical basis for the treatment of renal failure. 
      ABSTRACT: Hypoxia-reoxygenation (H/R) induction can affect miRNA expression and 
      then control NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated 
      pyroptosis. This study investigated the mechanism of miR-302a-3p in H/R-induced 
      renal tubular epithelial cell (RTEC) pyroptosis. Human HK-2 RTECs were induced by 
      H/R. Lactate dehydrogenase content, cell activity and pyroptosis, and levels of 
      NLRP3, GSDMD-N, caspase-1, interleukin (IL)-1beta, IL-18, superoxide dismutase, and 
      malondialdehyde were detected to verify the effect of H/R on HK-2 cells. The 
      NLRP3 inflammasome action was evaluated after H/R-induced HK-2 cells were treated 
      with BAY11-7082, an inflammasome inhibitor. After inhibiting miR-302a-3p 
      expression, the changes of pyroptosis were observed. The binding relation between 
      miR-302a-3p and FMRP translational regulator 1 (FMR1) was verified. A 
      function-rescue experiment verified the role of FMR1 in the regulation of 
      pyroptosis. H/R-induced HK-2 cells showed significant pyroptosis injury, and the 
      NLRP3 inflammasome was activated. After inhibiting the NLRP3 inflammasome, 
      H/R-induced apoptosis was inhibited. After H/R treatment, miR-302a-3p in HK-2 
      cells was increased, and miR-302a-3p downregulation limited H/R-induced NLRP3 
      inflammasome-mediated pyroptosis. FMR1 is the target of miR-302a-3p. Inhibition 
      of FMR1 alleviated the inhibition of H/R-induced HK-2 cell pyroptosis by 
      miR-302a-3p inhibitor. Collectively, inhibiting miR-302a-3p can weaken its 
      targeted inhibition on FMR1, thereby inhibiting the activation of NLRP3 
      inflammasomes and reducing caspase-1-dependent pyroptosis in HK-2 cells.
CI  - (c) 2021 The Authors. Experimental Physiology (c) 2021 The Physiological Society.
FAU - Bai, Tao
AU  - Bai T
AD  - Pathology Department, First Hospital of Shanxi Medical University, Taiyuan, 
      Shanxi, China.
FAU - Cui, Yanzhi
AU  - Cui Y
AD  - Medical oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, 
      Hebei, China.
FAU - Yang, Xian
AU  - Yang X
AD  - Pathology Department, First Hospital of Shanxi Medical University, Taiyuan, 
      Shanxi, China.
FAU - Cui, Xinyue
AU  - Cui X
AD  - Pathology Department, First Hospital of Shanxi Medical University, Taiyuan, 
      Shanxi, China.
FAU - Yan, Congmin
AU  - Yan C
AD  - Pathology Department, First Hospital of Shanxi Medical University, Taiyuan, 
      Shanxi, China.
FAU - Tang, Ying
AU  - Tang Y
AD  - Pathology Department, First Hospital of Shanxi Medical University, Taiyuan, 
      Shanxi, China.
FAU - Cao, Xiaoming
AU  - Cao X
AUID- ORCID: 0000-0002-3306-3468
AD  - Urology Department, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 
      China.
FAU - Dong, Chunhui
AU  - Dong C
AD  - Department of urinary surgery, Fourth Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211109
PL  - England
TA  - Exp Physiol
JT  - Experimental physiology
JID - 9002940
RN  - 0 (FMR1 protein, human)
RN  - 0 (Inflammasomes)
RN  - 0 (MIRN302A microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
SB  - IM
MH  - Epithelial Cells/metabolism
MH  - Fragile X Mental Retardation Protein/pharmacology
MH  - Humans
MH  - Hypoxia
MH  - Inflammasomes
MH  - *MicroRNAs/genetics/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - *Pyroptosis/genetics
OTO - NOTNLM
OT  - FMR1
OT  - NLRP3/caspase-1
OT  - hypoxia-reoxygenation
OT  - miR-302a-3p
OT  - pyroptosis
OT  - renal tubular epithelial cells
EDAT- 2021/10/05 06:00
MHDA- 2022/04/01 06:00
CRDT- 2021/10/04 06:29
PHST- 2021/07/12 00:00 [received]
PHST- 2021/09/29 00:00 [accepted]
PHST- 2021/10/05 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2021/10/04 06:29 [entrez]
AID - 10.1113/EP089887 [doi]
PST - ppublish
SO  - Exp Physiol. 2021 Dec;106(12):2531-2541. doi: 10.1113/EP089887. Epub 2021 Nov 9.