Puerarin Alleviates Lipopolysaccharide-Induced Myocardial Fibrosis by Inhibiting PARP-1 to Prevent HMGB1-Mediated TLR4-NF-κB Signaling Pathway.
Cardiovasc Toxicol
; 20(5): 482-491, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32236896
ABSTRACT
Myocardial fibrosis (MFs) is a crucial pathological process that results in cardiac failure in the development of multiple cardiovascular diseases. Puerarin could reportedly be used to treat a variety of cardiovascular diseases. However, the exact mechanism of puerarin on MFs was not clear enough. The separated primary cardiac fibroblasts (CFs) were induced by lipopolysaccharide (LPS) and treated with puerarin. The levels of TNF-α, IL-6, HMGB1, PARP-1, α-SMA, collagen-1, collagen-3, NF-κB pathways were examined by ELISA, immunofluorescence, RT-qPCR, western blot and immunohistochemistry assays. In addition, MFs rats' model was established using transverse aortic constriction (TAC), and the degree of fibrosis was certified by masson staining. We successfully separated primary CFs, and certified that LPS induction could upregulate the levels of PARP-1, HMGB1, inflammatory cytokines and fibrosis-related proteins (α-SMA, collagen-1 and collagen-3). In addition, we proved that puerarin could weaken MFs, and PARP-1 and HMGB1 expressions, which were induced by LPS in primary CFs. In terms of mechanism, HMGB1 expression could be promoted by PARP-1, and PARP-1 could attenuate the therapeutic effect of puerarin on LPS-induced MFs. Besides, PARP-1-HMGB1-NF-κB pathway was related to the protective effect of puerarin on MFs. In vivo, we also verified the protective efficacy of puerarin on MFs induced by TAC, and puerarin also regulated HMGB1-mediated TLR4-NF-κB signaling pathway. We demonstrated that puerarin could ameliorate MFs by downregulating PARP-1 to inhibit HMGB1-mediated TLR4-NF-κB signaling pathway in LPS-induced primary CFs and TAC-induced MFs rats' model.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
FN-kappa B
/
Proteína HMGB1
/
Receptor Toll-Like 4
/
Fibroblastos
/
Poli(ADP-Ribosa) Polimerasa-1
/
Isoflavonas
/
Antiinflamatorios
/
Cardiomiopatías
/
Miocardio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cardiovasc Toxicol
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
TOXICOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China