Interference with the expression of S1PR1 or STAT3 attenuates valvular damage due to rheumatic heart disease.
Int J Mol Med
; 48(3)2021 Sep.
Article
in En
| MEDLINE
| ID: mdl-34296288
ABSTRACT
Rheumatic heart disease (RHD) affects numerous individuals annually; however, its pathogenesis remains unclear. The sphingosine 1phosphate receptor 1 (S1PR1) and signal transducer and activator of transcription 3 (STAT3) have recently been shown to be involved in valvular damage via the promotion of the differentiation of T helper 17 (Th17) cells during the development of RHDinduced valvular damage. The present study investigated whether altering the expression of S1PR1 or STAT3 attenuates valvular damage due to RHD. Inactivated group A streptococcus (GAS) was used to establish a rat model of RHD. Recombinant adenoassociated viral vectors carrying an S1PR1 overexpression sequence were used to overexpress S1PR1. STAT3 small interfering RNA (STAT3siRNA) was used to inhibit STAT3 expression. Reverse transcriptionquantitative PCR (RTqPCR) was performed to detect the mRNA expression of S1PR1, STAT3, collagen type III α1 chain (Col3a1) and fibroblastspecific protein 1. Western blotting (WB) and immunohistochemistry were used to detect the levels of S1PR1, STAT3, phosphorylated (p) STAT3, and retinoic acidrelated orphan receptor γT (RORγt) proteins. Enzymelinked immunosorbent assays (ELISAs) and immunohistochemistry were used to detect the levels of interleukin (IL)6 and IL17. Hematoxylin and eosin (H&E) staining and Sirius Red staining were performed to evaluate the degree of inflammation and fibrosis in the valvular tissues. S1PR1 expression was decreased in the valvular tissues of the rats with RHD. The levels of IL6, IL17 and pSTAT3 in the rats with RHD were increased. The degree of valvular inflammation and fibrosis in the rats with RHD was also increased. The overexpression of S1PR1 and the inhibition of STAT3 reduced the total pSTAT3 level, resulting in decreased levels of IL6, IL17 and RORγt, and a reduced degree of valvular inflammation and fibrosis. These results suggest that the expression of S1PR1 and STAT3 may be involved in valvular tissue damage due to RHD. Thus, strategies designed to interfere with the expression of S1PR1 or STAT3 may affect the expression of Th17 cellrelated cytokines and may thus attenuate valvular damage due to RHD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rheumatic Heart Disease
/
STAT3 Transcription Factor
/
Sphingosine-1-Phosphate Receptors
/
Heart Valve Diseases
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int J Mol Med
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2021
Document type:
Article