The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis

Yan, Chao; Wang, Lin; Li, Bo; Zhang, Beibei; Zhang, Bo; Wang, Yanhong; Li, Xiangyang; Chen, Jiaxu; Tang, Renxian; Zheng, Kuiyang

doi:10.1186/s13071-015-0675-y

Cited by 51 publications

(41 citation statements)

References 34 publications

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“…In addition, the destruction of liver tissue structure caused by fibroblast proliferation and collagen deposition, and the destruction of bile duct structure that characterized with cholangiocyte hyperplasia, narrowing of bile duct lumen and periductal fibrosis were found (Figure1). These results were consistent with the typical pathological of C.sinensis infection as described in our previous research [15].…”

Section: Discussionsupporting

confidence: 93%

The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis

Yang

Qin

et al. 2019

Preprint

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Background Clonorchis sinensis infection could trigger strong immune responses in mice and human.However, whether the C.sinensis infection has an impact on arthritis is unknown. Here we investigated the effect of C.sinensis infection on type II collagen-induced arthritis in BALB/c mice. ResultsThe mice were firstly infected with 45 C.sinensis metacercariae by oral gavage. Four weeks later, the arthritis in mice was induced by type II collagen. Joint inflammation with severe redness and swelling in hind paws were observed in type II collagen-induced arthritis (CIA) mice. In addition, the physical activity was significantly reduced, but the respiratory exchange ratio was increased in CIA mice. Compared with CIA mice, C.sinensis infection could increase the severity of arthritis in CIA mice, based on the results of disease score and pathological changes. Compared to CIA mice, increased neutrophils and Ly6C hi monocytes, decreased B cells and CD4+T cells were found in C.sinensis infected CIA mice. Besides these, C.sinensis infected mice also displayed significant higher levels of serum IL-4 and IL-17 than those in CIA mice. Taken together, our data suggest that C.sinensis infection have a bad effect on arthritis, and could induce the abnormality of immune response in mice with CIA. BackgroundRheumatoid arthritis (RA) is a kind of autoimmune disease, which is characterized with chronic joint inflammation, synovial membranes proliferation and vasculogenesis, and could lead to the cartilage and bone destruction [1]. It is estimated that, 24.5 million people are effected by RA[2], and the published reports have been shown that the immune responses mediated by neutrophils, T cells, B cells, macrophages and associated cytokines, including TNF-α, interleukin (IL)-6, IL-17 and IL-1, play important roles in RA [3]. Therefore, further understanding the factors that could have an effect on the immune response in RA maybe help us find potential strategies for treatment of the disease.It is well known that parasitic infection is capable of inducing the host immune response towards a strong type 2 immune response, which is could be induced by the activation of Th2 cells with the secretion of IL-4, 5]. Besides these, T helper 17 (Th17) cells, Th9 and T regulatory (Treg) cells also participate in the immune response during parasitic infection [6]. Furthermore, current studies suggest that early infection of certain parasites may prevent the development of antoimmune diseases, including allergic disease and RA [7], and the mechanisms are associated with immune responses mediated by parasite infection. For example, it has been shown that Schistosoma japonicum infection and Trichinella spiralis derived antigen could reduce the severity of collageninduced arthritis [8], via immune reactions related to IL-4 and Treg Cells mediated by parasite antigens in CIA mice. Clonorchiasis, induced by clonorchis sinensis, is widely prevalent in Asian region, including China, Korea, Vietnam and the far east regions of Russia. Just like other helminth...

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Section: Discussionsupporting

confidence: 93%

The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis

Yang

Qin

et al. 2019

Preprint

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“…TGF‐β/Smad signalling is a canonical pathway which potently regulates tissue fibrogenesis . TGF‐β1 is known to play a central role in the pathogenesis and progression of renal fibrosis .…”

Section: Discussionmentioning

confidence: 99%

MiR‐101a ameliorates AngII‐mediated hypertensive nephropathy by blockade of TGFβ/Smad3 and NF‐κB signalling in a mouse model of hypertension

Ding

Zhou

Huang

2018

Clin Exp Pharma Physio

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Primary hypertension (essential hypertension or idiopathic hypertension) is regarded as the most common type of hypertension and affects 95% of hypertensive patients. 1 Primary hypertension is a crucial risk factor of cerebral, cardiac, and renal events. Moreover, hypertensive nephropathy is one of the most lethal complications of primary hypertension. Recently, more and more evidence has shown that high blood pressure may cause tubular cell damage and tubulointerstitial fibrosis. In addition, high blood pressure can also cause podocyte effacement and loss, which subsequently results in glomerular basement membrane denudation and adhesion to Bowman's capsule. 2 MicroRNAs (miRNAs or miRs) are small (about 22 nucleotides) noncoding RNAs which regulate gene expression via inhibiting translation or guiding corresponding target mRNA cleavage. 3 Emerging evidence indicates that many miRNAs are often involved in various Summary Hypertensive nephropathy, clinically characterized by progressive renal fibrosis and inflammation, is a severe complication of hypertension. The objectives of this study were to investigate the roles of miR-101a in relieving angiotensin II (Ang II)-mediated hypertensive nephropathy and uncover the possible underlying mechanisms. A hypertensive mouse model was established via continuous 28-day AngII infusion.Systolic blood pressure (SBP), ratio of urine albumin to creatinine, blood urea nitrogen (BUN), serum creatinine (Scr) and glomerular filtration rate (GFR) were evaluated.Dual luciferase reporter assay was used to explore the target of miR-101a. mRNA levels of miR-101a, TGFβRI, fibrotic markers (Collagen I and α-SMA) and pro-inflammatory cytokines (IL-1β and TNF-α) were determined by real-time PCR. Protein levels of TGFβRI, Collagen I, α-SMA, IL-1β, TNF-α, t-p65, P-p65, t-Smad3, P-Smad3, t-IκBα and P-IκBα were detected by western blot. MiR-101a mimics significantly improved GFR and inhibited AngII-induced increase in the ratio of urine albumin to creatinine, BUN and Scr. MiR-101a mimics partially abolished AngII-induced increase in the mRNA and protein level of fibrotic markers by targeting TGFβRI and inhibiting TGFβ/ Smad3 pathway. Moreover, TGFβRI inhibitor galunisertib inhibited AngII-mediated renal injury in mice with hypertensive nephropathy. Additionally, miR-101a overexpression blocked AngII-induced up-regulation of pro-inflammatory markers via suppressing NF-κB pathway. MiR-101a exhibited protective effects against hypertensive nephropathy via inhibiting TGFβ/Smad3 and NF-κB signalling pathways. K E Y W O R D SAngII, hypertensive nephropathy, miR-101a, NF-κB, TGFβRI

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“…Recent studies have demonstrated that TGF-β/Smad signaling plays a crucial role in the progression of hepatic fibrosis caused by parasitic infection, including Schistosoma , Clonorchis sinensis , and Echinococcus multilocularis , as well as other etiological factors[79,80]. More specifically, TGF-β1 ligation to TGF-β type I (TGFβRI) and type II receptors induces Smad2/3 phosphorylation and its subsequent interaction with Smad4.…”

Section: Novel Therapeutic Targets In Liver Fibrosismentioning

confidence: 99%

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

Zhang¹,

Yuan²,

He³

et al. 2016

WJG

466

327

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Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells (HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.

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The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis

Cited by 51 publications

References 34 publications

The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis

The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis

MiR‐101a ameliorates AngII‐mediated hypertensive nephropathy by blockade of TGFβ/Smad3 and NF‐κB signalling in a mouse model of hypertension

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

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