PMID- 36569120
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221227
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 9
DP  - 2022
TI  - Fibroblast growth factor 23 level modulates the hepatocyte's 
      alpha-2-HS-glycoprotein transcription through the inflammatory pathway TNFalpha/NFkappaB.
PG  - 1038638
LID - 10.3389/fmed.2022.1038638 [doi]
LID - 1038638
AB  - INTRODUCTION: High serum levels of fibroblast growth factor 23 (FGF23) 
      characterize chronic kidney disease (CKD) since its early stages and have been 
      suggested to contribute to inflammation and cardiovascular disease. However, the 
      mechanisms linking FGF23 with these pathological conditions remain still 
      incompletely defined. The alpha-2-HS-glycoprotein (AHSG), a liver-produced 
      anti-inflammatory cytokine, is highly modulated by inflammation itself, also 
      through the TNFalpha/NFkappaB signaling pathway. In our previous study, we found that 
      FGF23 modulates the production of AHSG in the liver in a bimodal way, with 
      stimulation and inhibition at moderately and highly increased FGF23 
      concentrations, respectively. METHODS: The present study, aiming to gain further 
      insights into this bimodal behavior, was performed in hepatocyte human cells line 
      (HepG2), using the following methods: immunochemistry, western blot, chromatin 
      immunoprecipitation, fluorescence in situ hybridization (FISH), qRT-PCR, and gene 
      SANGER sequencing. RESULTS: We found that FGF23 at 400 pg/ml activates nuclear 
      translocation of NFkappaB, possibly increasing AHSG transcription. At variance, at 
      1,200 pg/ml, FGF23 inactivates NFkappaB through the activation of two specific NFkappaB 
      inhibitors (IkappaBalpha and NKIRAS2) and induces its detachment from the AHSG promoter, 
      reducing AHSG transcription. CONCLUSION: These results add another piece to the 
      puzzle of FGF23 involvement in the multifold interactions between CKD, 
      inflammation, and cardiovascular disease, suggesting the involvement of the NFkappaB 
      pathway, which might represent a potential therapeutic target in CKD.
CI  - Copyright (c) 2022 Mattinzoli, Li, Castellano, Ikehata, Armelloni, Elli, Molinari, 
      Tsugawa, Alfieri and Messa.
FAU - Mattinzoli, Deborah
AU  - Mattinzoli D
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Renal Research 
      Laboratory, Milan, Italy.
FAU - Li, Min
AU  - Li M
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Renal Research 
      Laboratory, Milan, Italy.
FAU - Castellano, Giuseppe
AU  - Castellano G
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Nephrology, 
      Dialysis and Renal Transplant, Milan, Italy.
AD  - Department of Clinical Sciences and Community Health, University of Milan, Milan, 
      Italy.
FAU - Ikehata, Masami
AU  - Ikehata M
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Renal Research 
      Laboratory, Milan, Italy.
FAU - Armelloni, Silvia
AU  - Armelloni S
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Renal Research 
      Laboratory, Milan, Italy.
FAU - Elli, Francesca Marta
AU  - Elli FM
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Endocrinology Unit, 
      Milan, Italy.
FAU - Molinari, Paolo
AU  - Molinari P
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Nephrology, 
      Dialysis and Renal Transplant, Milan, Italy.
FAU - Tsugawa, Koji
AU  - Tsugawa K
AD  - Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
FAU - Alfieri, Carlo Maria
AU  - Alfieri CM
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Nephrology, 
      Dialysis and Renal Transplant, Milan, Italy.
AD  - Department of Clinical Sciences and Community Health, University of Milan, Milan, 
      Italy.
FAU - Messa, Piergiorgio
AU  - Messa P
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Nephrology, 
      Dialysis and Renal Transplant, Milan, Italy.
AD  - Department of Clinical Sciences and Community Health, University of Milan, Milan, 
      Italy.
LA  - eng
SI  - figshare/10.6084/m9.figshare.20980939
PT  - Journal Article
DEP - 20221207
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC9769965
OTO - NOTNLM
OT  - AHSG
OT  - FGF23
OT  - NFkappaB
OT  - cardiovascular disease
OT  - chronic kidney disease
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/12/27 06:00
MHDA- 2022/12/27 06:01
PMCR- 2022/12/07
CRDT- 2022/12/26 04:06
PHST- 2022/09/07 00:00 [received]
PHST- 2022/11/22 00:00 [accepted]
PHST- 2022/12/26 04:06 [entrez]
PHST- 2022/12/27 06:00 [pubmed]
PHST- 2022/12/27 06:01 [medline]
PHST- 2022/12/07 00:00 [pmc-release]
AID - 10.3389/fmed.2022.1038638 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2022 Dec 7;9:1038638. doi: 10.3389/fmed.2022.1038638. 
      eCollection 2022.