Pirfenidone prevents radiation-induced intestinal fibrosis in rats by inhibiting fibroblast proliferation and differentiation and suppressing the TGF-β1/Smad/CTGF signaling pathway

2018 ◽  
Vol 822 ◽  
pp. 199-206 ◽  
Author(s):  
Yan-Wu Sun ◽  
Yi-Yi Zhang ◽  
Xin-Jie Ke ◽  
Xue-jing Wu ◽  
Zhi-Fen Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Fibroblast Proliferation ◽  
Intestinal Fibrosis ◽  
Proliferation And Differentiation ◽  
Radiation Induced ◽  
Tgf Β1

Calycosin Inhibits Intestinal Fibrosis on CCD-18Co Cells via Modulating Transforming Growth Factor-β/Smad Signaling Pathway

Pharmacology ◽  
2019 ◽  
Vol 104 (1-2) ◽  
pp. 81-89 ◽  
Author(s):  
Jing Liu ◽  
Tan Deng ◽  
Yaxin Wang ◽  
Mengmeng Zhang ◽  
Guannan Zhu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Collagen I ◽  
Smad Pathway ◽  
Smad Signaling ◽  
Intestinal Fibrosis ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Background: Intestinal fibrosis is the major complication of Crohn’s disease (CD). There are no other good treatments for CD except surgery and remains a refractory disease. Calycosin (CA), the active component of astragalus membranaceus, has been reported the potential effect on lung fibrosis and renal fibrosis. In this study, we aim to explore the effect of CA on intestinal fibrosis in vitro and the possible signal pathway. Methods: The antifibrotic effect of CA is investigated in human intestinal fibroblasts (CCD-18Co) cells induced by transforming growth factor-β1 (TGF-β1). MTT method was used to screen the concentration of CA. Real-time polymerase chain reaction and western blot analysis were used to evaluate the expression of α-smooth muscle actin (α-SMA), collagen I, and TGF-β/Smad pathway. Results: The results showed that the concentration of CA was 12.5, 25, 50 μmol/L. CA could inhibit the expression of α-SMA and collagen I. In addition, CA regulated the expression of TGF-β/Smad signaling pathway. Conclusion: This study demonstrated that CA could inhibit the activation of CCD-18Co cells and reduce the expression of extracellular matrix. Our study highlighted that CA-inhibited TGF-β/Smad pathway through inhibiting the expression of p-Smad2, p-Smad3, Smad4, and TGF-β1 and raised the Smad7 expression. Therefore, CA might inhibit intestinal fibrosis by inhibiting the TGF-β/Smad pathway.

scholarly journals Glycyrrhetinic acid alleviates radiation-induced lung injury in mice

2017 ◽  
Vol 58 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Jinmei Chen ◽  
Weijian Zhang ◽  
Lurong Zhang ◽  
Jiemin Zhang ◽  
Xiuying Chen ◽  
...  
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Lung Tissue ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Glycyrrhetinic Acid ◽  
Control Group ◽  
X Rays ◽  
Radiation Induced ◽  
Tgf Β1

Abstract Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway.

scholarly journals Huangqi Shengmai Yin Protects against Radiation-Induced Cardiac Fibrosis Injury by Regulating the TGF-β1/Smads and MMPs

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Gu ◽  
Yongqi Liu ◽  
Hongyan Wu ◽  
Hailong Li ◽  
Kai Liu
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Cardiac Fibrosis ◽  
Volume Fraction ◽  
X Rays ◽  
Rat Hearts ◽  
Radiation Induced ◽  
First Time ◽  
Myocardial Pathology ◽  
Tgf Β1

Background. Radiation-induced heart damage is considered to be a progressive process of fibrosis. Emerging evidence has indicated that the Smads and matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMP) may be involved in radiation-induced cardiac fibrosis (RICF) by regulating the activation of TGF-β1 signaling pathway. Based on this, the present study was undertaken to characterize the effect of Huangqi Shengmai Yin (HSY) on RICF in a rat model. Methods. Precardiac region of rats was irradiated with 25 Gy X-rays, and their myocardial pathology scores in terms of injury and collagen volume fraction (CVF) and the expression levels of fibrotic molecules were detected. Results. The pathology scores and CVF in myocardial tissue increased after irradiation, and the expression of TGF-β1, Col1, and Col3 increased. This change indicated that such irradiation promoted the fibrosis damage in rat hearts. The damage was accompanied by an increase in the expression of Smad 2, Smad3, Smad4, and MMP14 and a decrease in the expression of Smad 7 and TIMP1. Administration of HSY weakened the RICF by decreasing pathology score and CVF and decreased the expression of TGF-β1, Col1, and Col3 in irradiated rat hearts. In addition, Smad2, Smad3, Smad4, and MMP14 were downregulated, while Smad 7 and TIMP1 were upregulated during intervention with HSY. Conclusions. The involvement of the TGF-β1/Smads and MMPs/TIMP system in RICF was confirmed. This study demonstrated, for the first time, that HSY attenuates the effects of RICF in a rat model. The effect HSY was found to be closely related to the TGF-β1/Smads signaling pathway and MMPs system. These results suggest that HSY is a prospective drug for clinical treatment of RICF.

scholarly journals Molecular aspects of chronic radiation enteritis

2011 ◽  
Vol 34 (3) ◽  
pp. 119 ◽  
Author(s):  
Yanfei Zhu ◽  
Jing Zhou ◽  
Guoqing Tao
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Tissue Growth ◽  
Radiation Enteritis ◽  
Intestinal Fibrosis ◽  
Chronic Radiation ◽  
Radiation Induced ◽  
Molecular Aspects ◽  
Tgf Β1

Purpose: Chronic radiation enteritis (CRE) is one of the most feared complications of abdominal or pelvic radiation therapy and the treatment of CRE is difficult and often controversial. Recent progress in molecular biology has shed some light on the pathogenesis of CRE, which is characterized by fibrosis. The purpose of this article is to summarize the current state of knowledge of molecular aspects of radiation induced intestinal fibrosis and to discuss potential therapeutic targets. Methods: A review of the up-to-date published literature involving the possible molecular cascades in radiation-induced intestinal fibrosis and prospective targets for CRE were performed using the Pub-Med search engine. Results: Fibrosis development is correlated with transforming growth factor β1 (TGF-β1) and its downstream effector Smad3, which stimulates fibrogenic downstream mediators, such as connective tissue growth factor (CTGF). Ras homologue (Rho) and Rho-associated kinase (ROCK) signaling pathway have been shown to play important roles in the development of CRE. The inhibition of these pathways ameliorated radiation-induced intestinal fibrosis in vitro and in animal studies; however, the relationship between the Smad3 and Rho signaling pathways has not been elucidated. Conclusions: Rho/ROCK and TGF-β1/Smad3 signaling pathways have been shown to play a key role in intestinal fibrogenesis, which might provide with effective possibilities for clinical intervention. Understanding the cooperation between Smad3 and Rho, may therefore be critical to our overall understanding of fibrosis development and maintenance of CRE.

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