PMID- 38345033
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240220
IS  - 1525-6049 (Electronic)
IS  - 0886-022X (Print)
IS  - 0886-022X (Linking)
VI  - 46
IP  - 1
DP  - 2024 Dec
TI  - Kruppel-like factor 4 modulates the miR-101/COL10A1 axis to inhibit renal 
      fibrosis after AKI by regulating epithelial-mesenchymal transition.
PG  - 2316259
LID - 10.1080/0886022X.2024.2316259 [doi]
LID - 2316259
AB  - Acute kidney injury (AKI) can progress to renal fibrosis and chronic kidney 
      disease (CKD), which reduces quality of life and increases the economic burden on 
      patients. However, the molecular mechanisms underlying renal fibrosis following 
      AKI remain unclear. This study tested the hypothesis that the Kruppel-like factor 
      4 (KLF4)/miR-101/Collagen alpha-1X (COL10A1) axis could inhibit 
      epithelial-mesenchymal transition (EMT) and renal fibrosis after AKI in a mouse 
      model of ischemia-reperfusion (I/R)-induced renal fibrosis and HK-2 cells by gene 
      silencing, overexpression, immunofluorescence, immunohistochemistry, real-time 
      quantitative PCR, Western blotting, dual-luciferase reporter assay, fluorescence 
      in situ hybridization (FISH) and ELISA. Compared with the Sham group, I/R induced 
      renal tubular and glomerular injury and fibrosis, and increased the levels of 
      BUN, serum Scr and neutrophil gelatinase-associated lipocalin (NGAL), Col10a1 and 
      Vimentin expression, but decreased E-cadherin expression in the kidney tissues of 
      mice at 42 days post-I/R. Similarly, hypoxia promoted fibroblastic morphological 
      changes in HK-2 cells and enhanced NGAL, COL10A1, Vimentin, and alpha-SMA expression, 
      but reduced E-cadherin expression in HK-2 cells. These pathological changes were 
      significantly mitigated in COL10A1-silenced renal tissues and HK-2 cells. KLF4 
      induces miR-101 transcription. More importantly, hypoxia upregulated Vimentin and 
      COL10A1 expression, but decreased miR-101, KLF4, and E-cadherin expression in 
      HK-2 cells. These hypoxic effects were significantly mitigated or abrogated by 
      KLF4 over-expression in the HK-2 cells. Our data indicate that KLF4 up-regulates 
      miR-101 expression, leading to the downregulation of COL10A1 expression, 
      inhibition of EMT and renal fibrosis during the pathogenic process of I/R-related 
      renal fibrosis.
FAU - Zhao, Jingying
AU  - Zhao J
AD  - Department of Pediatrics, Shengjing Hospital of China Medical University, 
      Shenyang, People's Republic of China.
FAU - Wang, Xiuli
AU  - Wang X
AD  - Department of Pediatrics, Shengjing Hospital of China Medical University, 
      Shenyang, People's Republic of China.
FAU - Wu, Yubin
AU  - Wu Y
AD  - Department of Pediatrics, Shengjing Hospital of China Medical University, 
      Shenyang, People's Republic of China.
FAU - Zhao, Chengguang
AU  - Zhao C
AD  - Department of Pediatrics, Shengjing Hospital of China Medical University, 
      Shenyang, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20240212
PL  - England
TA  - Ren Fail
JT  - Renal failure
JID - 8701128
RN  - 0 (MicroRNAs)
RN  - 0 (Lipocalin-2)
RN  - 0 (Vimentin)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Cadherins)
RN  - 9007-34-5 (Collagen)
RN  - 0 (MIRN101 microRNA, human)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *MicroRNAs/metabolism
MH  - Lipocalin-2
MH  - Vimentin/metabolism
MH  - Kruppel-Like Factor 4
MH  - In Situ Hybridization, Fluorescence
MH  - Quality of Life
MH  - Cadherins/metabolism
MH  - *Acute Kidney Injury/genetics
MH  - Epithelial-Mesenchymal Transition
MH  - Collagen/metabolism
MH  - Fibrosis
MH  - Hypoxia
PMC - PMC10863509
OTO - NOTNLM
OT  - COL10A1
OT  - EMT
OT  - KLF4
OT  - miR-101
OT  - renal fibrosis
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2024/02/12 15:44
MHDA- 2024/02/12 15:45
PMCR- 2024/02/12
CRDT- 2024/02/12 07:57
PHST- 2024/02/12 15:45 [medline]
PHST- 2024/02/12 15:44 [pubmed]
PHST- 2024/02/12 07:57 [entrez]
PHST- 2024/02/12 00:00 [pmc-release]
AID - 2316259 [pii]
AID - 10.1080/0886022X.2024.2316259 [doi]
PST - ppublish
SO  - Ren Fail. 2024 Dec;46(1):2316259. doi: 10.1080/0886022X.2024.2316259. Epub 2024 
      Feb 12.