PMID- 32019767
OWN - NLM
STAT- MEDLINE
DCOM- 20210728
LR  - 20210728
IS  - 1708-8267 (Electronic)
IS  - 1081-5589 (Print)
IS  - 1081-5589 (Linking)
VI  - 68
IP  - 4
DP  - 2020 Apr
TI  - CLCN5 5'UTR isoforms in human kidneys: differential expression analysis between 
      controls and patients with glomerulonephritis.
PG  - 864-869
LID - 10.1136/jim-2019-001205 [doi]
AB  - ClC-5, the electrogenic chloride/proton exchanger strongly expressed in renal 
      proximal tubules, belongs to the endocytic macromolecular complex responsible for 
      albumin and low-molecular-weight protein uptake. ClC-5 was found to be 
      overexpressed in glomeruli of glomerulonephritis and in cultured human podocytes 
      under albumin overload. The transcriptional regulation of human ClC-5 is not 
      fully understood. Three functional promoters of various strengths and 11 
      different 5' untranslated region (5'UTR) isoforms of CLCN5 messenger RNA (mRNA) 
      were detected in the human kidney (variants 1-11). The aim of this study was to 
      investigate the expression pattern of CLCN5 5'UTR variants and the CLCN5 common 
      translated region in glomerulonephritis. The 5'UTR ends and the translated region 
      of CLCN5 mRNA were analyzed using quantitative relative real-time PCR or 
      quantitative comparative endpoint PCR with GAPDH as housekeeping gene in 8 normal 
      kidneys and 12 renal biopsies from patients with glomerulonephritis. The 
      expression profile for all variants in normal and glomerulonephritis biopsies was 
      similar, and variant 3 and alternative variant 4 were the most abundantly 
      expressed in both sets. In glomerulonephritis biopsies, isoforms under the 
      control of a weak promoter (variants 4, 6 and 7) showed an increased expression 
      leading to an increase in the CLCN5 translated region, underscoring their 
      importance in kidney pathophysiology. Since weak promoters can be turned on by 
      different stimuli, these data support the hypothesis that proteinuria could be 
      one of the stimuli capable of starting a signaling pathway that induces an 
      increase in CLCN5 transcription.
CI  - (c) American Federation for Medical Research 2020. No commercial re-use. See rights 
      and permissions. Published by BMJ.
FAU - Ceol, Monica
AU  - Ceol M
AUID- ORCID: 0000-0001-7489-2433
AD  - Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology 
      Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy 
      monica.ceol@unipd.it.
FAU - Gianesello, Lisa
AU  - Gianesello L
AUID- ORCID: 0000-0001-9327-397X
AD  - Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology 
      Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy.
FAU - Tosetto, Enrica
AU  - Tosetto E
AD  - Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology 
      Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy.
FAU - Priante, Giovanna
AU  - Priante G
AUID- ORCID: 0000-0002-1870-4466
AD  - Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology 
      Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy.
FAU - Del Prete, Dorella
AU  - Del Prete D
AUID- ORCID: 0000-0003-2141-3472
AD  - Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology 
      Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy.
FAU - Anglani, Franca
AU  - Anglani F
AUID- ORCID: 0000-0003-1534-4458
AD  - Kidney Histomorphology and Molecular Biology Laboratory, Clinical Nephrology 
      Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy.
LA  - eng
GR  - U54 DK083908/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200203
PL  - England
TA  - J Investig Med
JT  - Journal of investigative medicine : the official publication of the American 
      Federation for Clinical Research
JID - 9501229
RN  - 0 (5' Untranslated Regions)
RN  - 0 (CLC-5 chloride channel)
RN  - 0 (Chloride Channels)
RN  - 0 (Protein Isoforms)
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - Aged
MH  - Biopsy
MH  - Case-Control Studies
MH  - Chloride Channels/*genetics/metabolism
MH  - Female
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Glomerulonephritis/*genetics/pathology
MH  - Humans
MH  - Kidney/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Protein Isoforms/genetics/metabolism
PMC - PMC7402611
MID - NIHMS1610362
OTO - NOTNLM
OT  - CLCN5
OT  - 5'UTR
OT  - gene expression
OT  - isoforms
OT  - proteinuria
COIS- Competing interests: None declared.
EDAT- 2020/02/06 06:00
MHDA- 2021/07/29 06:00
PMCR- 2020/08/04
CRDT- 2020/02/06 06:00
PHST- 2020/01/03 00:00 [accepted]
PHST- 2020/02/06 06:00 [pubmed]
PHST- 2021/07/29 06:00 [medline]
PHST- 2020/02/06 06:00 [entrez]
PHST- 2020/08/04 00:00 [pmc-release]
AID - jim-2019-001205 [pii]
AID - 10.1136/jim-2019-001205 [doi]
PST - ppublish
SO  - J Investig Med. 2020 Apr;68(4):864-869. doi: 10.1136/jim-2019-001205. Epub 2020 
      Feb 3.