PMID- 29843125
OWN - NLM
STAT- MEDLINE
DCOM- 20181022
LR  - 20240412
IS  - 1423-0143 (Electronic)
IS  - 1420-4096 (Linking)
VI  - 43
IP  - 3
DP  - 2018
TI  - Mucin 4 Gene Silencing Reduces Oxidative Stress and Calcium Oxalate Crystal 
      Formation in Renal Tubular Epithelial Cells Through the Extracellular 
      Signal-Regulated Kinase Signaling Pathway in Nephrolithiasis Rat Model.
PG  - 820-835
LID - 10.1159/000490136 [doi]
AB  - BACKGROUND/AIMS: Nephrolithiasis plagues a great number of patients all over the 
      world. Increasing evidence shows that the extracellular signal-regulated kinase 
      (ERK) signaling pathway and renal tubular epithelial cell (RTEC) dysfunction and 
      attrition are central to the pathogenesis of kidney diseases. Mucin 4 (MUC4) is 
      reported as an activator of ERK signaling pathway in epithelial cells. In this 
      study, using rat models of calcium oxalate (CaOx) nephrolithiasis, the present 
      study aims to define the roles of MUC4 and ERK signaling pathway as contributors 
      to oxidative stress and CaOx crystal formation in RTEC. METHODS: Data sets of 
      nephrolithiasis were searched using GEO database and a heat flow map was drawn. 
      Then MUC4 function was predicted. Wistar rats were prepared for the purpose of 
      model establishment of ethylene glycol and ammonium chloride induced CaOx 
      nephrolithiasis. In order to assess the detailed regulatory mechanism of MUC4 
      silencing on the ERK signaling pathway and RTEC, we used recombinant plasmid to 
      downregulate MUC4 expression in Wistar rat-based models. Samples from rat urine, 
      serum and kidney tissues were reviewed to identify oxalic acid and calcium 
      contents, BUN, Cr, Ca2+ and P3+ levels, calcium crystal formation in renal 
      tubules and MUC4 positive expression rate. Finally, RT-qPCR, Western blot 
      analysis, and ELISA were employed to access oxidative stress state and CaOx 
      crystal formation in RTEC. RESULTS: Initially, MUC4 was found to have an 
      influence on the process of nephrolithiasis. MUC4 was upregulated in the CaOx 
      nephrolithiasis model rats. We proved that the silencing of MUC4 triggered the 
      inactivation of ERK signaling pathway. Following the silencing of MUC4 or the 
      inhibition of ERK signaling pathway, the oxalic acid and calcium contents in rat 
      urine, BUN, Cr, Ca2+ and P3+ levels in rat serum, p-ERK1/2, MCP-1 and OPN 
      expressions in RTEC and H2O2 and MDA levels in the cultured supernatant were 
      downregulated, but the GSH-Px, CAT and SOD levels in the cultured supernatant 
      were increased. Moreover, MUC4 silencing or ERK signaling pathway inactivation 
      may decrease the formation of CaOx crystals. CONCLUSION: Taken together, 
      silencing of MUC4 can inactivate the ERK signaling pathway and further restrain 
      oxidative stress and CaOx crystal formation in RTEC. Thus, MUC4 represents a 
      potential investigative focus target in nephrolithiasis.
CI  - (c) 2018 The Author(s). Published by S. Karger AG, Basel.
FAU - Sun, Ling
AU  - Sun L
AD  - Department of Nephrology, Xuzhou Central Hospital, Medical College of Southeast 
      University, Xuzhou, China, slpku@163.com.
FAU - Zou, Lu-Xi
AU  - Zou LX
AD  - School of Management, Zhejiang University, Hangzhou, China.
FAU - Wang, Jie
AU  - Wang J
AD  - Department of Nephrology, Xuzhou Central Hospital, Medical College of Southeast 
      University, Xuzhou, China.
FAU - Chen, Ting
AU  - Chen T
AD  - Department of Nephrology, Xuzhou Central Hospital, Medical College of Southeast 
      University, Xuzhou, China.
FAU - Han, Yu-Chen
AU  - Han YC
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University, Nanjing, China.
FAU - Zhu, Dong-Dong
AU  - Zhu DD
AD  - Institute of Nephrology, Zhongda Hospital, Southeast University, Nanjing, China.
FAU - Zhuo, Shi-Chao
AU  - Zhuo SC
AD  - Department of Pathology, Xuzhou Central Hospital, Medical College of Southeast 
      University, Xuzhou, China.
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20180525
PL  - Switzerland
TA  - Kidney Blood Press Res
JT  - Kidney & blood pressure research
JID - 9610505
RN  - 0 (Mucin-4)
RN  - 2612HC57YE (Calcium Oxalate)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - Nephrolithiasis, Calcium Oxalate
SB  - IM
RIN - Kidney Blood Press Res. 2022;47(9):592. PMID: 37335011
MH  - Animals
MH  - Calcium Oxalate/*analysis
MH  - Epithelial Cells/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Gene Silencing
MH  - Kidney Tubules/pathology
MH  - Mucin-4/*genetics
MH  - Nephrolithiasis/*etiology
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Calcium oxalate crystal formation
OT  - Extracellular signal-regulated kinase signaling pathway
OT  - Mucin 4
OT  - Nephrolithiasis
OT  - Oxidative stress
OT  - Renal tubular epithelial cell
EDAT- 2018/05/31 06:00
MHDA- 2018/10/23 06:00
CRDT- 2018/05/30 06:00
PHST- 2018/02/09 00:00 [received]
PHST- 2018/05/17 00:00 [accepted]
PHST- 2018/05/31 06:00 [pubmed]
PHST- 2018/10/23 06:00 [medline]
PHST- 2018/05/30 06:00 [entrez]
AID - 000490136 [pii]
AID - 10.1159/000490136 [doi]
PST - ppublish
SO  - Kidney Blood Press Res. 2018;43(3):820-835. doi: 10.1159/000490136. Epub 2018 May 
      25.