Puerarin Alleviates Lipopolysaccharide-Induced Myocardial Fibrosis by Inhibiting PARP-1 to Prevent HMGB1-Mediated TLR4-N
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Puerarin Alleviates Lipopolysaccharide‑Induced Myocardial Fibrosis by Inhibiting PARP‑1 to Prevent HMGB1‑Mediated TLR4‑NF‑κB Signaling Pathway Shu‑Yuan Ni1,2 · Xing‑Long Zhong1 · Ze‑Hua Li1 · Dong‑Jian Huang2 · Wen‑Ting Xu2 · Yan Zhou2 · Cai‑Wen Ou3 · Min‑Sheng Chen1
© Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Puerarin · Myocardial fibrosis · PARP-1 · HMGB1 · Lipopolysaccharide
Introduction Handling Editor: Y. James Kang. * Min‑Sheng Chen [email protected] 1
Guangdong Provincial Center of Biomedical Engineering for Cardiovascular Diseases, Zhujiang Hospital, Southern Medical University, No. 1023, Shatai Nan Road, Guangzhou 510280, China
2
Department of Intensive Care Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
3
Key Laboratory of Construction and Detection of Guangdong Province, Guangdong Provincial Center of Biomedical Engineering for Cardiovascular Diseases, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
Myocardial fibrosis (MFs) is the most familiar pathological feature of ischemic cardiovascular disease [1]. MFs could be caused by myocardial infarction, arrhythmias, acute myocardial ischemia, heart failure, inflammation and aging [2, 3]. Research have certified that MFs can lead to abnormal cardiac conduction, impair
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