OL-026 Dickkopf-1 down-regulates transforming growth factor-β1 induced hepatic stellate cells activation

Li, W.T.; Xiao, Zhihong; Zhu, Cheng; Li, Y.; Gao, Runping

doi:10.1016/s1201-9712(11)60085-4

Cited by 8 publications

(10 citation statements)

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“…In addition, the proliferation and migration of HSCs after activation effectively amplify the fibrotic response. Furthermore, profibrotic cytokines and growth factors secreted by activated HSCs (like transforming growth factor- β [TGF- β ], platelet-derived growth factor [PDGF], matrix metalloproteinases [MMPs], epidermal growth factor [EGF], leptin, and so on [4–9]) perpetuate the fibrotic process through paracrine and autocrine effects.…”

Section: Discussionmentioning

confidence: 99%

“…Following a fibrogenic stimulus, the HSCs change from quiescent vitamin A-storing cells to activated myofibroblast-like cells with ECM increasing dramatically, especially type I collagen. Besides secreting ECM, activated HSCs also produce a number of profibrotic cytokines and growth factors to both maintain and deteriorate the fibrotic process in paracrine and autocrine ways [4–9]. So HSCs may be a good target for prevention and treatment of liver fibrosis.…”

Section: Introductionmentioning

confidence: 99%

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miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway

Wang

Huang

et al. 2017

BioMed Research International

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Background Although expression of miR-200s is aberrant in liver fibrosis, its role in liver fibrogenesis still remains unknown. Here, we investigated the role of miR-200c in the activation of human hepatic stellate cells (HSCs) and induction of liver fibrosis. Methods We engineered human HSCs (LX2 cell line) to stably express miR-200c (LX2-200c) or empty vector control (LX2-nc). Results miR-200c expression upregulated α-smooth muscle actin (SMA) and vimentin, enhanced HSCs growth and migration, increased expression of collagen type I (a main component of ECM) gene and secretion of epidermal growth factor (EGF), and upregulated the phosphorylation of Akt, a downstream effector of the PI3K pathway. As a target of miR-200s and inhibitor of PI3K pathway, FOG2 protein expression was significantly suppressed in LX2-200c cells. Moreover, LY294002, a highly selective inhibitor of PI3K, blocked phosphorylation of Akt and the effects of miR-200c. Conclusions These data suggest that miR-200c activates HSCs in liver fibrosis possibly by downregulating FOG2 protein expression and upregulating PI3K/Akt signaling. Autocrine activation of EGF signaling may also be a mechanism of miR-200c-mediated HSCs activation. So miR-200c can be a potential marker for HSCs activation and liver fibrosis progression, as well as a potential target to attenuate liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway

Wang

Huang

et al. 2017

BioMed Research International

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“…26 Preventing HSC activation therefore represents a promising treatment strategy. 27 Agn is abundant and cost-friendly, and can inhibit smooth muscle cell proliferation and fibroblast mediated collagen synthesis. 24,28,29 However, how Agn effects hepatic fibrosis has not been studied.…”

Section: Discussionmentioning

confidence: 99%

<p>Alginate Suppresses Liver Fibrosis Through the Inhibition of Nuclear Factor-κB Signaling</p>

Xia¹,

Ding²,

Zheng³

et al. 2020

DDDT

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Purpose: Liver fibrosis (or liver scarring) is a causative factor for hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Alginate (Agn) isolated from brown algae is known to slow the proliferation of fibroblasts, through the mechanisms of these effects remain undefined. This study explored the benefits of Agn on hepatic health and its associated mechanism(s) of action in hepatic stellate cells (HSC-T6s). Materials and Methods: To assess the effects of Agn, HSC-T6s were treated with PDGF and cell proliferation, colony formation, cell migration, cell invasiveness and apoptosis were assessed. Rat models of liver fibrosis were produced through 12-week injections of intraperitoneal (IP) carbon tetrachloride (CCl 4 ). Rats were Agn-treated from weeks 8 to 12, and liver damage was assessed through Masson's and H Materials and Methods: & E staining. Gene expression profiles were assayed via RT-PCR, Western blot and commercial ELISA kits. Results: Agn reduced the proliferation of HSC-T6s and increased apoptotic rates through the downregulation of the Bcl-2:Bax ratio. Agn also inhibited the invasion and migration of HSC-T6s, prevented ECM deposition, and reduced the occurrence of liver fibrosis in rat models. Agn also prevented IκBα and p65 phosphorylation. Conclusion: Agn prevents liver fibrosis through its attenuation of HSC activation and division through the suppression of NF-κB in in vitro and animal models. This highlights how the clinical use of Agn can prevent hepatic fibrosis.

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“…miR-144 deficiency interrupts ECM remodeling and decreases left ventricular remodeling following myocardial infarction leading to worsened cardiac function (26,27). Notably, bleomycin-induced pulmonary fibrosis has been demonstrated to be associated with miR-144 expression (38), while miR-144 induces hepatic stellate cell activation in the human fibrotic liver by targeting TGF-β1 (39) and regulates relaxin/insulin-like family peptide receptor 1 expression in lung fibroblasts (40). Overall, these results indicate that miR-144 may play an important role in the fibrotic progression underlying various diseases.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑144 regulates angiotensin II‑induced cardiac fibroblast activation by targeting CREB

Liu

et al. 2020

Exp Ther Med

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Cardiac fibrosis is involved in adverse cardiac remodeling and heart failure, which is the leading cause of deteriorated cardiac function. Accumulative evidence has elucidated that microRNAs (miRNAs) play important roles in the pathogenesis of cardiac fibrosis. However, the exact molecular mechanism underlying miR-144 in cardiac fibrosis remains unknown. In the present study, a transverse aortic constriction (TAC) mouse model and angiotensin II (Ang II)-induced cardiac fibroblasts (CFs) were constructed in order to investigate the expression levels of miR-144. It was demonstrated that miR-144 was significantly downregulated following pathological stimuli. CFs infected with miR-144 mimics were then used to test the effect of miR-144 on CF activation in vitro. The results revealed that overexpression of miR-144 led to a dramatically decreased proliferation and migration ability in CFs, as well as the transformation from fibroblasts to myofibroblasts, which was characterized by the decreased expression of collagen-I, collagen-III, CTGF, fibronectin and α-SMA. By contrast, such effects could be reversed by miR-144 knockdown. Mechanistically, the bioinformatics analysis and luciferase reporter assay in the present study demonstrated that cAMP response element-binding protein (CREB) was a direct target of miR-144, and the expression of CREB was attenuated by miR-144. The results of the present study demonstrated that miR-144 played a key role in CF activation, partially by targeting CREB, which further suggested that the overexpression of miR-144 may be a promising strategy for the treatment of cardiac fibrosis.

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OL-026 Dickkopf-1 down-regulates transforming growth factor-β1 induced hepatic stellate cells activation

Cited by 8 publications

References 0 publications

miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway

miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway

<p>Alginate Suppresses Liver Fibrosis Through the Inhibition of Nuclear Factor-κB Signaling</p>

MicroRNA‑144 regulates angiotensin II‑induced cardiac fibroblast activation by targeting CREB

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