Inhibition of STAT3 alleviates LPS-induced apoptosis and inflammation in renal tubular epithelial cells by transcriptionally down-regulating TASL.
Eur J Med Res
; 29(1): 34, 2024 Jan 06.
Article
em En
| MEDLINE
| ID: mdl-38184662
ABSTRACT
BACKGROUND:
Systemic lupus erythematosus (SLE) is a common autoimmune disease that impacts various organs. Lupus nephritis (LN) significantly contributes to death in children with SLE. Toll-like receptor (TLR) adaptor interacting with SLC15A4 on the lysosome (TASL) acts as an innate immune adaptor for TLR and is implicated in the pathogenesis of SLE. A transcription factor known as signal transducer and activator of transcription 3 (STAT3), which is known to be linked to autoimmune diseases, is also involved in the development of SLE.METHODS:
Bioinformatics and real-time quantitative PCR (qRT-PCR) was used to detect the expression of STAT3 and TASL in peripheral blood of SLE patients and their correlation. Bioinformatics analysis, qRT-PCR, luciferase assay and chromatin immunoprecipitation (ChIP) were used to verify the regulation of transcription factor STAT3 on TASL. The expression levels of STAT3, TASL and apoptosis-related genes in LPS-induced HK2 cells were detected by qRT-PCR and Western blot. TUNEL staining were used to detect the apoptosis of HK2 cells after LPS stimulation. ELISA and qRT-PCR were used to detect the levels of inflammatory cytokines in the cell culture supernatant. TASL knockdown in HK2 cells was used to detect the changes in apoptosis-related genes and inflammatory factors. The expression level of TASL in LPS-stimulated HK2 cells and its effect on cell apoptosis and inflammatory factors were observed by knocking down and overexpressing STAT3, respectively. It was also verified in a rescue experiment.RESULTS:
The expressions of STAT3 and TASL were higher in SLE than in healthy children, and the expression of STAT3 was positively correlated with TASL. Transcription factor STAT3 can directly and positively regulate the expression of TASL through the promoter region binding site. The expression of STAT3, TASL and inflammatory cytokines was elevated, and the change of apoptosis was up-regulated in LPS-stimulated HK2 cells. Inhibition of STAT3 alleviates LPS-stimulated apoptosis and inflammatory response in HK2 cells through transcriptional regulation of TASL.CONCLUSIONS:
These findings provide new insights into the transcriptional regulation of TASL and provide new evidence of a direct regulatory relationship between signaling nodes in the lupus signaling network.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nefrite Lúpica
/
Lúpus Eritematoso Sistêmico
Limite:
Child
/
Humans
Idioma:
En
Revista:
Eur J Med Res
Ano de publicação:
2024
Tipo de documento:
Article