PMID- 38315030
OWN - NLM
STAT- MEDLINE
DCOM- 20240306
LR  - 20240307
IS  - 2165-0497 (Electronic)
IS  - 2165-0497 (Linking)
VI  - 12
IP  - 3
DP  - 2024 Mar 5
TI  - Hepatitis B virus-targeting sodium taurocholate cotransporting polypeptide 
      mediates HBV infection and damage in human renal podocytes.
PG  - e0136523
LID - 10.1128/spectrum.01365-23 [doi]
LID - e01365-23
AB  - Hepatitis B virus (HBV) may directly infect human podocytes (HPCs). However, the 
      mechanism of direct infection is unclear. We found that HPCs express sodium 
      taurocholate cotransporting polypeptide (NTCP), a specific receptor for HBV entry 
      into hepatocytes. Thus, we investigated whether NTCP mediates HBV infection and 
      damage in HPCs and further clarified the specific mechanism. We constructed 
      shRNA-NTCP1,2, shRNA-NC, WT-NTCP, and MUT-NTCP and transfected them into HPCs. 
      HPCs were infected with HBV, and HBV infection markers were detected by 
      enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR 
      (RT-qPCR). The functional changes in HPCs were detected by Transwell migration 
      and scratch assays, apoptosis was evaluated by flow cytometry (FCM), and 
      podocytoskeletal proteins (nephrin, CD2AP, and synaptopodin) were determined by 
      western blotting (WB). Compared with the control HPCs, HPCs infected with HBV 
      showed increased levels of HBV infection markers and apoptosis along with 
      decreased podocytoskeletal protein expressions, cell vitality, proliferation, and 
      migration. Compared with the HPCs infected with HBV, the HPCs transfected with 
      HBV + shRNA-NTCP, and HBV + MUT-NTCP showed decreased levels of HBV infection 
      markers and apoptosis along with increased podocytoskeletal protein expressions, 
      cell vitality, proliferation, and migration; the opposite effects were observed 
      in the HPCs transfected with HBV + WT-NTCP. Overall, the changes to NTCP affected 
      the susceptibility of HPCs to HBV and modulated HPC damage and repair. NTCP can 
      mediate direct HBV infection and damage human podocytes, and the NTCP 157-165 
      locus is the main site of HBV entry. The findings provide a new target and 
      theoretical basis for HBV-associated glomerulonephritis. IMPORTANCE: This study 
      identified for the first time that sodium taurocholate cotransporting polypeptide 
      (NTCP) can mediate HBV direct infection and damage to human podocytes, and the 
      NTCP157-165 locus is the main HBV entry site. The findings provide theoretical 
      support for the pathogenesis of direct infection of HBV with kidney tissue. The 
      findings provide a new target and theoretical basis for the treatment of 
      HBV-related glomerulonephritis (HBV-GN). Blocking NTCP is a new target for the 
      treatment of HBV-GN. We found that tacrolimus, a calcineurin inhibitor that 
      blocks NTCP, can effectively treat HBV-GN. This study also provides a theoretical 
      basis for the effective and safe treatment of immunosuppressant tacrolimus for 
      HBV-GN.
FAU - Wang, Lifen
AU  - Wang L
AUID- ORCID: 0009-0009-0536-4333
AD  - Department of Nephrology, Shenzhen Hospital of Southern Medical University, 
      Shenzhen, China.
FAU - Wang, Cheng
AU  - Wang C
AD  - Department of Nephrology, Shenzhen Hospital of Southern Medical University, 
      Shenzhen, China.
FAU - Wang, Xu
AU  - Wang X
AD  - Department of Nephrology, Shenzhen Hospital of Southern Medical University, 
      Shenzhen, China.
FAU - Cao, Yantao
AU  - Cao Y
AD  - Department of Nephrology, Shenzhen Hospital of Southern Medical University, 
      Shenzhen, China.
FAU - Guo, Xiaohua
AU  - Guo X
AUID- ORCID: 0009-0001-2022-1084
AD  - Department of Nephrology, Shenzhen Hospital of Southern Medical University, 
      Shenzhen, China.
FAU - Ye, Zhiming
AU  - Ye Z
AUID- ORCID: 0009-0009-9389-8182
AD  - Department of Nephrology, Guangdong Academy of Medical Sciences, Guangdong 
      Provincial People's Hospital, Guangzhou, China.
LA  - eng
GR  - 81600575/MOST | National Natural Science Foundation of China (NSFC)/
GR  - 2060404/Guangzhou Science, Technology and Innovation Commission (Bureau of 
      Science and Information Technology of Guangzhou Municipality)/
PT  - Journal Article
DEP - 20240205
PL  - United States
TA  - Microbiol Spectr
JT  - Microbiology spectrum
JID - 101634614
RN  - 145420-23-1 (sodium-bile acid cotransporter)
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - 0 (Organic Anion Transporters, Sodium-Dependent)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Symporters)
SB  - IM
MH  - Humans
MH  - Hepatitis B virus/genetics
MH  - Tacrolimus/metabolism
MH  - *Podocytes/metabolism
MH  - *Hepatitis B
MH  - Organic Anion Transporters, Sodium-Dependent/genetics/metabolism
MH  - *Glomerulonephritis
MH  - RNA, Small Interfering
MH  - *Symporters
PMC - PMC10913464
OTO - NOTNLM
OT  - NTCP
OT  - glomerulonephritis
OT  - hepatitis B virus
OT  - podocytes
COIS- The authors declare no conflict of interest.
EDAT- 2024/02/05 14:44
MHDA- 2024/03/06 06:43
PMCR- 2024/02/05
CRDT- 2024/02/05 09:04
PHST- 2024/03/06 06:43 [medline]
PHST- 2024/02/05 14:44 [pubmed]
PHST- 2024/02/05 09:04 [entrez]
PHST- 2024/02/05 00:00 [pmc-release]
AID - 01365-23 [pii]
AID - spectrum.01365-23 [pii]
AID - 10.1128/spectrum.01365-23 [doi]
PST - ppublish
SO  - Microbiol Spectr. 2024 Mar 5;12(3):e0136523. doi: 10.1128/spectrum.01365-23. Epub 
      2024 Feb 5.