PMID- 32768584
OWN - NLM
STAT- MEDLINE
DCOM- 20200930
LR  - 20200930
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 258
DP  - 2020 Oct 1
TI  - Endothelin converting enzyme-1 (ECE-1) deletion in association with Endothelin-1 
      downregulation ameliorates kidney fibrosis in mice.
PG  - 118223
LID - S0024-3205(20)30975-9 [pii]
LID - 10.1016/j.lfs.2020.118223 [doi]
AB  - Kidney fibrosis is a common final pathway of chronic kidney diseases, which are 
      characterized by renal architecture damage, inflammation, fibroblast expansion 
      and myofibroblast formation. Endothelin converting enzyme-1 (ECE-1) contributes 
      to activation of Endothelin-1 (ET-1), a potent vasoconstrictor and pro-fibrotic 
      substance. This study elucidated the effect of ECE-1 knockout in kidney fibrosis 
      model in mice in association of ET-1 downregulation. Kidney fibrosis was 
      performed in ECE-1 knockout (ECE-1 KO) and vascular endothelial derived ET-1 KO 
      (VEETKO) mice (2 months, 20-30 g, n = 30) and their wild type (WT) littermates 
      using unilateral ureteral obstruction (UUO) procedure. Mice were euthanized on 
      day-7 and day-14 after UUO. Histopathological analysis was conducted for fibrosis 
      and tubular injury. Immunostainings were done to quantify macrophages (F4/80), 
      fibroblasts (FSP-1) and myofibroblasts (alpha-SMA). Monocyte Chemoattractant 
      Protein-1 (MCP-1), ECE-1 and preproET-1 (ppET-1) mRNA expression were quantified 
      with qRT-PCR, while Transforming Growth Factor-beta1 (TGF-beta1) and alpha-SMA protein 
      level were quantified with Western blot. ECE-1 KO mice demonstrated reduction of 
      ECE-1 and ppET-1 mRNA expression, attenuation of kidney fibrosis, tubular injury, 
      MCP-1 mRNA expression and macrophage number compared to WT. Double immunostaining 
      revealed fibroblast to myofibroblast formation after UUO, while ECE-1 KO mice had 
      significantly lower fibroblast number and myofibroblast formation compared to WT, 
      which were associated with significantly lower TGF-beta1 and alpha-SMA protein levels in 
      day-14 of UUO. VEETKO mice also demonstrated attenuation of ET-1 protein level, 
      fibrosis and myofibroblast formation. In conclusion, ECE-1 knockout and ET-1 
      downregulation attenuated kidney fibrosis.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Arfian, Nur
AU  - Arfian N
AD  - Department of Anatomy, Faculty of Medicine, Public Health and Nursing, 
      Universitas Gadjah Mada, Yogyakarta, Indonesia. Electronic address: 
      nur_arfian@ugm.ac.id.
FAU - Suzuki, Yoko
AU  - Suzuki Y
AD  - Laboratory of Clinical Pharmaceutical Science, Kobe Pharmaceutical University, 
      Kobe, Japan. Electronic address: suzukiy@kobepharma-u.ac.jp.
FAU - Hartopo, Anggoro Budi
AU  - Hartopo AB
AD  - Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public 
      Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia. Electronic 
      address: a_bhartopo@ugm.ac.id.
FAU - Anggorowati, Nungki
AU  - Anggorowati N
AD  - Department of Anatomical Pathology, Faculty of Medicine, Public Health, and 
      Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia. Electronic address: 
      nungki@ugm.ac.id.
FAU - Nugrahaningsih, Dwi Aris Agung
AU  - Nugrahaningsih DAA
AD  - Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and 
      Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia. Electronic address: 
      dwi.aris.a@ugm.ac.id.
FAU - Emoto, Noriaki
AU  - Emoto N
AD  - Laboratory of Clinical Pharmaceutical Science, Kobe Pharmaceutical University, 
      Kobe, Japan; Division of Cardiovascular Medicine, Department of Internal 
      Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic 
      address: emoto@kobepharma-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20200805
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Endothelin-1)
RN  - EC 3.4.24.71 (Ece1 protein, mouse)
RN  - EC 3.4.24.71 (Endothelin-Converting Enzymes)
SB  - IM
MH  - Animals
MH  - Down-Regulation/*physiology
MH  - Endothelin-1/*metabolism
MH  - Endothelin-Converting Enzymes/*deficiency/genetics
MH  - Fibrosis
MH  - Kidney/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
OTO - NOTNLM
OT  - Endothelin converting enzyme-1 (ECE-1)
OT  - Endothelin-1
OT  - Fibroblast
OT  - Inflammation
OT  - Kidney fibrosis
OT  - Myofibroblast
COIS- Declaration of competing interest The authors declare that there are no conflicts 
      of interest.
EDAT- 2020/08/10 06:00
MHDA- 2020/10/02 06:00
CRDT- 2020/08/10 06:00
PHST- 2020/04/16 00:00 [received]
PHST- 2020/08/01 00:00 [revised]
PHST- 2020/08/03 00:00 [accepted]
PHST- 2020/08/10 06:00 [pubmed]
PHST- 2020/10/02 06:00 [medline]
PHST- 2020/08/10 06:00 [entrez]
AID - S0024-3205(20)30975-9 [pii]
AID - 10.1016/j.lfs.2020.118223 [doi]
PST - ppublish
SO  - Life Sci. 2020 Oct 1;258:118223. doi: 10.1016/j.lfs.2020.118223. Epub 2020 Aug 5.