scholarly journals Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-β/SMAD Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan Xu ◽  
Xiaobo Qu ◽  
Jia Zhou ◽  
Guangfu Lv ◽  
Dong Han ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Myocardial Injury ◽  
Pathological Examination ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Expression Levels ◽  
Smad Signaling ◽  
Protein Levels ◽  
Smad Signaling Pathway

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.

Forsythiaside B inhibits myocardial fibrosis via down regulating TGF-β1/Smad signaling pathway

2021 ◽  
pp. 174354
Author(s):  
Jing Sun ◽  
Jiaxin Zhu ◽  
Lei Chen ◽  
Bingjing Duan ◽  
Ruyi Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis through inhibition of the myocardial NF-κB/TGF-β1/Smad signaling pathway

2019 ◽  
Vol 10 (2) ◽  
pp. 1179-1190 ◽  
Author(s):  
Jia Wang ◽  
Wei Shen ◽  
Jun-Yan Zhang ◽  
Chang-Hao Jia ◽  
Mei-Lin Xie
Keyword(s):  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Antioxidant Ability ◽  
Smad Signaling ◽  
Synergistic Inhibition ◽  
Smad Signaling Pathway ◽  
Smad7 Expression ◽  
Tgf Β1

Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis, and its mechanisms are associated with the increments of antioxidant ability, PPARγ activation, and Smad7 expression, which cause a synergistic inhibition of the NF-κB/TGF-β1/Smad signaling pathway.

scholarly journals Effects of MiR-375-BMPR2 as a Key Factor Downstream of BMP15/GDF9 on the Smad1/5/8 and Smad2/3 Signaling Pathways

2018 ◽  
Vol 46 (1) ◽  
pp. 213-225 ◽  
Author(s):  
Chang Liu ◽  
Bao Yuan ◽  
Hongyan Chen ◽  
Mingqiang Xu ◽  
Xulei Sun ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cumulus Cell ◽  
Cumulus Cells ◽  
Cell Counting ◽  
Type I ◽  
Type Ii ◽  
Expression Levels ◽  
Smad Signaling ◽  
Proliferation And Apoptosis ◽  
Smad Signaling Pathway

Background/Aims: Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), which are secreted by oocytes, are important regulators of follicular growth and development and ovarian function. These two factors can regulate the proliferation and apoptosis of cumulus cells via modulation of the Smad signaling pathway. Studies have shown that BMP15 and GDF9 can affect the level of miR-375, whereas the target gene of miR-375 is BMPR2, the type II receptor of BMP15 and GDF9. However, whether or how the BMP15/ GDF9-miR-375-BMPR2 pathway affects the proliferation and apoptosis of bovine cumulus cells through regulation of the Smad signaling pathway remains unclear. Methods: In this study, cumulus cells were first obtained from cumulus-oocyte complexes (COCs). Appropriate concentrations of BMP15 and GDF9 were added during the in vitro culture process. Cell Counting Kit-8 (CCK-8) analyses and flow cytometry were used to determine the effects of BMP15/GDF9 on bovine cumulus cells proliferation and apoptosis. Subsequently, miR-375 mimics, miR-375 inhibitor and BMPR2 siRNA were synthesized and used for transfection experiments. Western Blot analysis was used to detect changes before and after transfection in the expression levels of the BMP15/GDF9 type I receptors ALK4, ALK5 and ALK6; the phosphorylation levels of Smad2/3 and Smad1/5/8, which are key signaling pathway proteins downstream of BMP15/GDF9; the expression levels of PTX3, HAS2 and PTGS2, which are key genes involved in cumulus cells proliferation; and Bcl2/Bax, which are genes involved in apoptosis. Results: The addition of 100 ng/mL BMP15 or 200 ng/mL GDF9 or the combined addition of 50 ng/mL BMP15 and 100 ng/mL GDF9 effectively inhibited bovine cumulus cell apoptosis and promoted cell proliferation. BMP15/GDF9 negatively regulated miR-375 expression and positively regulated BMPR2 expression. High levels of miR-375 and inhibition of BMPR2 resulted in increased expression of ALK4 and decreased expression of PTX3, HAS2 and PTGS2, whereas miR-375 inhibition resulted in the opposite results. BMP15 and GDF9 significantly activated the levels of p-Smad2/3 and p-Smad1/5/8, whereas miR-375 inhibited the levels of p-Smad2/3 and p-Smad1/5/8 by negatively regulating BMPR2 and also led to apoptosis. Conclusion: BMP15 and GDF9 have synergistic effects and can act through miR-375 to affect the expression levels of type I receptor ALK4 and type II receptor BMPR2 and the activation of Smad signaling pathway, which subsequently affected the proliferation, spread and apoptosis of cumulus cells.

scholarly journals Salvanic acid B inhibits myocardial fibrosis through regulating TGF-β1/Smad signaling pathway

2019 ◽  
Vol 110 ◽  
pp. 685-691 ◽  
Author(s):  
Hongyan Gao ◽  
Zhe Bo ◽  
Qin Wang ◽  
Ling Luo ◽  
Haiyi Zhu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Inhibitory Effect of Corilagin on miR-21-Regulated Hepatic Fibrosis Signaling Pathway

2019 ◽  
Vol 47 (07) ◽  
pp. 1541-1569 ◽  
Author(s):  
Xuan Zhou ◽  
Jun Xiong ◽  
Shi Lu ◽  
Lei Luo ◽  
Zhi-Lin Chen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Type I ◽  
Loss Of Function ◽  
Smad Signaling ◽  
Protein Levels ◽  
Smad Signaling Pathway ◽  
Liver Tissues

Corilagin is a polyphenol that can be extracted from many medicinal plants and shows multiple pharmacological effects. We aimed to investigate the role of corilagin on miR-21-regulated hepatic fibrosis, especially miR-21-regulated TGF-[Formula: see text]1/Smad signaling pathway, in hepatic stellate LX2 cell line and Sprague–Dawley rats. The mRNA or protein levels of miR-21, Smad7, connective tissue growth factor (CTGF), [Formula: see text]-smooth muscle actin ([Formula: see text]-SMA), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), collagen type I alpha 1 (COL1A1), Smad2, Smad3, Smad2/3, p-Smad2, p-Smad3, p-Smad2/3, and transforming growth factor-[Formula: see text]1 (TGF-[Formula: see text]1) in LX2 cells and liver tissues were determined. Furthermore, gain-of and loss-of function of miR-21 in miR-21-regulated TGF-[Formula: see text]1/Smad signaling pathway were analyzed in LX2 cells. Liver tissues and serum were collected for pathological analysis, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Corilagin treatment reduced mRNA or protein levels of miR-21, CTGF, [Formula: see text]-SMA, TIMP-1, TGF-[Formula: see text]1, COL1A1, p-Smad2, p-Smad3, and p-Smad2/3 both in vitro and in vivo. While corilagin increased mRNA and protein levels of Smad7 and MMP-9. After gain-of and loss-of function of miR-21, the downstream effectors of miR-21-regulated TGF-[Formula: see text]1/Smad signaling pathway in LX2 cells changed accordingly, and the changes were inhibited by corilagin. Simultaneously, administration of corilagin not only ameliorated pathological manifestation of liver fibrosis but also reduced levels of [Formula: see text]-SMA and COL1A1 in liver tissues and TGF-[Formula: see text]1, ALT levels in serum. Corilagin is able to potentially prevent liver fibrosis by blocking the miR-21-regulated TGF-[Formula: see text]1/Smad signaling pathway in LX2 cells and CCl4-induced liver fibrosis rats, which may provide a novel therapeutic strategy for liver fibrosis.

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