PMID- 35058790
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220122
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 12
DP  - 2021
TI  - circHIPK3 Exacerbates Folic Acid-Induced Renal Tubulointerstitial Fibrosis by 
      Sponging miR-30a.
PG  - 715567
LID - 10.3389/fphys.2021.715567 [doi]
LID - 715567
AB  - Renal tubulointerstitial fibrosis is a common pathological feature of progressive 
      chronic kidney disease (CKD), and current treatment has limited efficacy. The 
      circular RNA circHIPK3 is reported to participate in the pathogenesis of various 
      human diseases. However, the role of circHIPK3 in renal fibrosis has not been 
      examined. In this study, we aimed to determine whether and how circHIPK3 might 
      participate in the pathogenesis of renal fibrosis. Mice received a peritoneal 
      injection of folic acid (250 mg/kg). Of note, 30 days later, renal fibrosis was 
      present on periodic acid-Schiff (PAS) and Masson staining, and mRNA and protein 
      of profibrotic genes encoding fibronectin (FN) and collagen 1 (COL1) were 
      increased. Renal circHIPK3 was upregulated, while miR-30a was downregulated, 
      assessed by quantitative PCR (qPCR) and fluorescence in situ hybridization 
      (FISH). The expression of transforming growth factor beta-1 (TGF-beta1) was 
      increased by qPCR analysis, immunoblotting, and immunofluorescence. Renal 
      circHIPK3 negatively correlated with miR-30a, and kidney miR-30a negatively 
      correlated with TGF-beta1. Target Scan and miRanda algorithms predicted three 
      perfect binding sites between circHIPK3 and miR-30a. We found that circHIPK3, 
      miR-30a, and TGF-beta1 colocalized in the cytoplasm of human tubular epithelial 
      cells (HK-2 cells) on FISH and immunofluorescence staining. We transfected 
      circHIPK3 and a scrambled RNA into HK-2 cells; miR-30a was downregulated, and the 
      profibrotic genes such as TGF-beta1, FN, and COL1 were upregulated and assessed by 
      qPCR, immunoblotting, and immunofluorescence staining. Third, the upregulation of 
      circHIPK3, downregulation of miR-30a, and overproduction of profibrotic FN and 
      COL1 were also observed in HK-2 cells exposed to TGF-beta1. Finally, renal biopsies 
      from patients with chronic tubulointerstitial nephritis manifested similar 
      expression patterns of circHIPK3, miR-30a, and profibrotic proteins, such as 
      TGF-beta1, FN, and COL1 as observed in the experimental model. A feed-forward cycle 
      was observed among circHIPK3, miR-30a, and TGF-beta1. Our results suggest that 
      circHIPK3 may contribute to progressive renal fibrosis by sponging miR-30a. 
      circHIPK3 may be a novel therapeutic target for slowing CKD progression.
CI  - Copyright (c) 2022 Wu, Luan, Jiao, Zhang, Ma, Zhang, Fu, Lai, Kopp, Pi and Zhou.
FAU - Wu, Yan
AU  - Wu Y
AD  - Department of Nephrology, Shengjing Hospital of China Medical University, 
      Shenyang, China.
FAU - Luan, Junjun
AU  - Luan J
AD  - Department of Nephrology, Shengjing Hospital of China Medical University, 
      Shenyang, China.
FAU - Jiao, Congcong
AU  - Jiao C
AD  - Department of Nephrology, Shengjing Hospital of China Medical University, 
      Shenyang, China.
FAU - Zhang, Shiwen
AU  - Zhang S
AD  - Department of Critical Care Medicine, Fushun Central Hospital, Fushun, China.
FAU - Ma, Cong
AU  - Ma C
AD  - Department of Nephrology, Shengjing Hospital of China Medical University, 
      Shenyang, China.
FAU - Zhang, Yixiao
AU  - Zhang Y
AD  - Department of Urology, Shengjing Hospital of China Medical University, Shenyang, 
      China.
FAU - Fu, Jingqi
AU  - Fu J
AD  - Program of Environmental Toxicology, School of Public Health, China Medical 
      University, Shenyang, China.
FAU - Lai, En Yin
AU  - Lai EY
AD  - Department of Physiology, School of Basic Medical Sciences, Zhejiang University 
      School of Medicine, Hangzhou, China.
FAU - Kopp, Jeffrey B
AU  - Kopp JB
AD  - Kidney Disease Section, NIDDK, NIH, Bethesda, MD, United States.
FAU - Pi, Jingbo
AU  - Pi J
AD  - Program of Environmental Toxicology, School of Public Health, China Medical 
      University, Shenyang, China.
FAU - Zhou, Hua
AU  - Zhou H
AD  - Department of Nephrology, Shengjing Hospital of China Medical University, 
      Shenyang, China.
LA  - eng
PT  - Journal Article
DEP - 20220104
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC8763699
OTO - NOTNLM
OT  - TGF-beta1
OT  - circHIPK3
OT  - miR-30a
OT  - renal biopsy
OT  - renal fibrosis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/01/22 06:00
MHDA- 2022/01/22 06:01
PMCR- 2022/01/04
CRDT- 2022/01/21 06:18
PHST- 2021/05/27 00:00 [received]
PHST- 2021/11/24 00:00 [accepted]
PHST- 2022/01/21 06:18 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/01/22 06:01 [medline]
PHST- 2022/01/04 00:00 [pmc-release]
AID - 10.3389/fphys.2021.715567 [doi]
PST - epublish
SO  - Front Physiol. 2022 Jan 4;12:715567. doi: 10.3389/fphys.2021.715567. eCollection 
      2021.