PMID- 30755642
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20200831
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Feb 12
TI  - Novel function of PiT1/SLC20A1 in LPS-related inflammation and wound healing.
PG  - 1808
LID - 10.1038/s41598-018-37551-1 [doi]
LID - 1808
AB  - PiT1/SLC20A1 is an inorganic phosphate transporter with additional functions 
      including the regulation of TNFalpha-induced apoptosis, erythropoiesis, cell 
      proliferation and insulin signaling. Recent data suggest a relationship between 
      PiT1 and NF-kappaB-dependent inflammation: (i) Pit1 mRNA is up-regulated in the 
      context of NF-kappaB pathway activation; (ii) NF-kappaB target gene transcription is 
      decreased in PiT1-deficient conditions. This led us to investigate the role of 
      PiT1 in lipopolysaccharide (LPS)-induced inflammation. MCP-1 and IL-6 
      concentrations were impaired in PiT1-deficient bone marrow derived macrophages 
      (BMDMs) upon LPS stimulation. Lower MCP-1 and IL-6 serum levels were observed in 
      Mx1-Cre; Pit1(lox/lox) mice dosed intraperitoneally with LPS. Lower PiT1 
      expression correlated with decreased in vitro wound healing and lower reactive 
      oxygen species levels. Reduced IkappaB degradation and lower p65 nuclear 
      translocation were observed in PiT1-deficient cells stimulated with LPS. 
      Conversely, PiT1 expression was induced in vitro upon LPS stimulation. Addition 
      of an NF-kappaB inhibitor abolished LPS-induced PiT1 expression. Furthermore, we 
      showed that p65 expression activated Pit1 promoter activity. Finally, ChIP assays 
      demonstrated that p65 directly binds to the mPit1 promoter in response to LPS. 
      These data demonstrate a completely novel function of PiT1 in the response to LPS 
      and provide mechanistic insights into the regulation of PiT1 expression by NF-kappaB.
FAU - Koumakis, Eugenie
AU  - Koumakis E
AD  - INSERM UMR_S1151 CNRS UMR8253 Institut Necker-Enfants Malades (INEM) Universite 
      Paris Descartes, Paris, France. eugenie.koumakis@aphp.fr.
AD  - Rheumatology Department, Cochin Hospital, APHP, Paris, France. 
      eugenie.koumakis@aphp.fr.
AD  - Centre de Reference des Maladies Rares du Metabolisme du Calcium et du Phosphate, 
      site constitutif, Cochin Hospital, Paris, France. eugenie.koumakis@aphp.fr.
FAU - Millet-Botti, Joelle
AU  - Millet-Botti J
AD  - INSERM UMR_S1151 CNRS UMR8253 Institut Necker-Enfants Malades (INEM) Universite 
      Paris Descartes, Paris, France.
AD  - Universite Paris Diderot-Sorbonne Paris Cite, F-75993, Paris, France.
FAU - Benna, Jamel El
AU  - Benna JE
AD  - INSERM U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, Universite 
      Paris Diderot, Sorbonne Paris Cite, Laboratoire d'Excellence Inflamex, Faculte de 
      Medecine, Site Xavier Bichat, 75018, Paris, France.
FAU - Leroy, Christine
AU  - Leroy C
AD  - INSERM UMR_S1151 CNRS UMR8253 Institut Necker-Enfants Malades (INEM) Universite 
      Paris Descartes, Paris, France.
FAU - Boitez, Valerie
AU  - Boitez V
AD  - INSERM UMR_S1151 CNRS UMR8253 Institut Necker-Enfants Malades (INEM) Universite 
      Paris Descartes, Paris, France.
FAU - Codogno, Patrice
AU  - Codogno P
AD  - INSERM UMR_S1151 CNRS UMR8253 Institut Necker-Enfants Malades (INEM) Universite 
      Paris Descartes, Paris, France.
FAU - Friedlander, Gerard
AU  - Friedlander G
AD  - INSERM UMR_S1151 CNRS UMR8253 Institut Necker-Enfants Malades (INEM) Universite 
      Paris Descartes, Paris, France.
FAU - Forand, Anne
AU  - Forand A
AD  - Inovarion, Paris, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190212
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Pit1 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Slc20a1 protein, mouse)
RN  - 0 (Sodium-Phosphate Cotransporter Proteins, Type III)
RN  - 0 (Thioglycolates)
RN  - 0 (Transcription Factor Pit-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Inflammation/*chemically induced/*metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - NADPH Oxidase 2/metabolism
MH  - NF-kappa B/metabolism
MH  - Peritonitis/chemically induced
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - Sodium-Phosphate Cotransporter Proteins, Type III/*metabolism
MH  - Thioglycolates/toxicity
MH  - Transcription Factor Pit-1/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Wound Healing/drug effects
PMC - PMC6372663
COIS- The authors declare no competing interests.
EDAT- 2019/02/14 06:00
MHDA- 2020/09/01 06:00
PMCR- 2019/02/12
CRDT- 2019/02/14 06:00
PHST- 2018/05/02 00:00 [received]
PHST- 2018/11/27 00:00 [accepted]
PHST- 2019/02/14 06:00 [entrez]
PHST- 2019/02/14 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2019/02/12 00:00 [pmc-release]
AID - 10.1038/s41598-018-37551-1 [pii]
AID - 37551 [pii]
AID - 10.1038/s41598-018-37551-1 [doi]
PST - epublish
SO  - Sci Rep. 2019 Feb 12;9(1):1808. doi: 10.1038/s41598-018-37551-1.