Novel function of PiT1/SLC20A1 in LPS-related inflammation and wound healing.
Sci Rep
; 9(1): 1808, 2019 02 12.
Article
in En
| MEDLINE
| ID: mdl-30755642
ABSTRACT
PiT1/SLC20A1 is an inorganic phosphate transporter with additional functions including the regulation of TNFα-induced apoptosis, erythropoiesis, cell proliferation and insulin signaling. Recent data suggest a relationship between PiT1 and NF-κB-dependent inflammation (i) Pit1 mRNA is up-regulated in the context of NF-κB pathway activation; (ii) NF-κB 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; Pit1lox/lox mice dosed intraperitoneally with LPS. Lower PiT1 expression correlated with decreased in vitro wound healing and lower reactive oxygen species levels. Reduced IκB 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-κB 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-κB.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lipopolysaccharides
/
Sodium-Phosphate Cotransporter Proteins, Type III
/
Transcription Factor Pit-1
/
Inflammation
Limits:
Animals
Language:
En
Journal:
Sci Rep
Year:
2019
Document type:
Article
Affiliation country:
Francia
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
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UK
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UNITED KINGDOM