PMID- 33993842
OWN - NLM
STAT- MEDLINE
DCOM- 20211111
LR  - 20220423
IS  - 1525-6049 (Electronic)
IS  - 0886-022X (Print)
IS  - 0886-022X (Linking)
VI  - 43
IP  - 1
DP  - 2021 Dec
TI  - Blocking core fucosylation of epidermal growth factor (EGF) receptor prevents 
      peritoneal fibrosis progression.
PG  - 869-877
LID - 10.1080/0886022X.2021.1918557 [doi]
AB  - OBJECTIVE: Peritoneal fibrosis (PF) ultimately causes ultrafiltration failure and 
      peritoneal dialysis (PD) termination, but there are few effective therapies for 
      it. Core fucosylation, which is catalyzed by alpha1,6-fucosyltransferase (Fut8) in 
      mammals, may play a crucial role in PF development. This study aims to assess the 
      effects of inhibiting core fucosylation of epidermal growth factor (EGF) receptor 
      on PF rats. METHODS: PF rats (established by 4.25% glucose dialysate) were 
      treated with either an adenovirus-Fut8 short hairpin RNA (Fut8shRNA) or 
      adenovirus-control. Masson's staining and net ultrafiltration were performed at 
      week six. Fut8 level and core fucosylation of EGF receptor and collagen I in the 
      peritoneal membrane were assessed, and EGF signaling was detected, including 
      signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa 
      B (NF-kappaB) and their phosphorylation. Monocyte chemoattractant protein-1 (MCP-1) 
      in peritoneal effluent was examined. RESULTS: Fut8 was upregulated in PF rats but 
      decreased after Fut8shRNA treatment. EGF and EGF receptor expression was 
      upregulated in PF rats, while core fucosylation of EGF receptor decreased after 
      Fut8shRNA treatment. Masson's staining results showed an increase in peritoneal 
      thickness in PF rats but a decrease after Fut8shRNA treatment. Fut8shRNA 
      treatment increased net ultrafiltration, reduced the expression of collagen I and 
      MCP-1 compared to PF rats. Fut8shRNA treatment suppressed phosphorylation of 
      STAT3 and NF-kappaB in the peritoneal membrane of PF rats. CONCLUSIONS: Fut8shRNA 
      treatment ameliorated the fibrotic changes in PF rats. A potential mechanism may 
      be that Fut8shRNA treatment inactivated EGF signaling pathway by suppressing the 
      phosphorylation of STAT3 and NF-kappaB.
FAU - Yu, Changqing
AU  - Yu C
AD  - Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, 
      First Affiliated Hospital of Dalian Medical University, Dalian, China.
FAU - Yang, Ning
AU  - Yang N
AD  - Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, 
      First Affiliated Hospital of Dalian Medical University, Dalian, China.
FAU - Wang, Weidong
AU  - Wang W
AD  - Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, 
      First Affiliated Hospital of Dalian Medical University, Dalian, China.
FAU - Du, Xiangning
AU  - Du X
AD  - Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, 
      First Affiliated Hospital of Dalian Medical University, Dalian, China.
FAU - Tang, Qingzhu
AU  - Tang Q
AD  - Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, 
      First Affiliated Hospital of Dalian Medical University, Dalian, China.
FAU - Lin, Hongli
AU  - Lin H
AD  - Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, 
      First Affiliated Hospital of Dalian Medical University, Dalian, China.
FAU - Li, Longkai
AU  - Li L
AUID- ORCID: 0000-0003-0607-4978
AD  - Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, 
      First Affiliated Hospital of Dalian Medical University, Dalian, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Ren Fail
JT  - Renal failure
JID - 8701128
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dialysis Solutions)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.4.1.- (Fucosyltransferases)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/metabolism
MH  - Dialysis Solutions
MH  - Disease Models, Animal
MH  - ErbB Receptors/drug effects/*metabolism
MH  - Fucosyltransferases/genetics/*pharmacology
MH  - Glycosylation/*drug effects
MH  - Male
MH  - Peritoneal Dialysis/*methods
MH  - Peritoneal Fibrosis/metabolism/pathology/*prevention & control
MH  - Peritoneum/drug effects/*metabolism/pathology
MH  - Phosphorylation
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
PMC - PMC8143636
OTO - NOTNLM
OT  - Core fucosylation
OT  - epidermal growth factor receptor
OT  - peritoneal dialysis
OT  - peritoneal fibrosis
COIS- The authors declare that they have no conflicts of interest regarding the 
      publication of this manuscript.
EDAT- 2021/05/18 06:00
MHDA- 2021/11/12 06:00
PMCR- 2021/05/17
CRDT- 2021/05/17 05:31
PHST- 2021/05/17 05:31 [entrez]
PHST- 2021/05/18 06:00 [pubmed]
PHST- 2021/11/12 06:00 [medline]
PHST- 2021/05/17 00:00 [pmc-release]
AID - 1918557 [pii]
AID - 10.1080/0886022X.2021.1918557 [doi]
PST - ppublish
SO  - Ren Fail. 2021 Dec;43(1):869-877. doi: 10.1080/0886022X.2021.1918557.