Wnt'er in liver: Expression of Wnt and frizzled genes in mouse

Zeng, Gang; Awan, Farrukh T.; Otruba, Wade; Müller, Peggy; Apte, Udayan; Tan, Xinping; Gandhi, Chandrashekhar R.; Demetris, Anthony J.; Monga, Satdarshan P.

doi:10.1002/hep.21473

Cited by 132 publications

(118 citation statements)

References 72 publications

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“…In contrast, little is known about the cells secreting the WNT3/4/5 and sFRP1/5 factors within liver tissues, and additional studies would be warranted to identify them as active and/or resting states of various cell types within the liverthat is, hepatocytes, biliary epithelial, sinusoidal endothelial, stellate, and Kupffer cells -as previously described in normal mouse livers (Zeng G et al, 2007). Finally, we have described for the first time that different potential FZD activating events occurring in many human HCC tissues and associated with the activation of different FZD-dependent pathways, which may play a role in hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

et al. 2008

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Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the b-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT -PCR in 62 human HCC of different etiologies and their matched peritumorous areas. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (b-catenin, protein kinase C, and C-Jun NH 2 -terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

et al. 2008

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“…However, this study identified the presence of Fzb (sFRP1) only in the activated cells, suggesting modulation of Wnt signaling during stellate or Kupffer cell activation. 3 Additional analysis would be imperative and would have strong clinical implications because of limited existing available therapeutic opportunities.…”

Section: Wnt Signaling and Hepatic Fibrosismentioning

confidence: 99%

“…Our laboratory has recently identified 11 Wnts and 9 Frizzleds that are normally expressed in an adult mouse liver. 3 Furthermore, a differential expression of these genes was observed in various cell types within the liver (Fig. 2).…”

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confidence: 99%

WNT/β‐catenin signaling in liver health and disease

2007

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Wnt/␤-catenin signaling is emerging as a forerunner for its critical roles in many facets of human biology. Its roles in embryogenesis, organogenesis, and maintaining tissue and organ homeostasis demonstrate its munificent character. Its roles in pathological conditions such as cancer and other human disorders such as inflammatory disorders and fibrosis reveal its villainous disposition. In liver, it also maintains its dual personality and is clearly of essence in several physiological events such as development, regeneration, and growth. Its aberrant activation is also evident in many different tumors of the liver, and recent studies are beginning to identify its role in additional hepatic pathological conditions. It is contributing to liver physiology and pathology by regulating various basic cellular events, including differentiation, proliferation, survival, oxidative stress, morphogenesis, and others. This review discusses the contribution of the Wnt/␤-catenin signaling pathway in these events and simultaneously provides an essential overview of the major developments in the field of Wnt/␤-catenin and liver pathobiology. In addition, areas that are currently deficient or understudied are identified and discussed along with the avenues of translational and clinical relevance. (HEPATOLOGY 2007;45:1298-1305

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“…Restored expression of PPARγ and/or other adipogenic transcription genes can reverse myofibroblastic HSCs to differentiated cells. The expression of adipogenic transcription factors has been shown to be essential for the maintenance of HSC quiescence in vitro [20][21][22]. Wnt signal pathway in vertebrate is a homologous gene and the translated proteins could participate in the regulation of cell proliferation, cell polarity and cell differentiation.…”

Section: Preventing and Treatment Of Liver Fibrosismentioning

confidence: 99%

Liver Fibrosis: Causes and Methods of Assessment, A Review

Toosi

2015

Romanian Journal of Internal Medicine

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Hepatic fibrogenesis is the final result of injury to the liver. Fibrosis could lead to hepatic dysfunction, important in the pathogenesis of other chronic problems. Therefore, understanding the mechanism, accurate diagnosis and staging of it in early stages accelerates the treatment and reduces the prevalence of chirrosis. Treatment strategies of liver problems and detction methods depend on the amount and progression of liver fibrosis and the rate of cirrhosis development. Traditionally the invasive method, liver biopsy, is reference standard to follow progression and stage of fibrosis. However, during the past decade, progressive development of novel non-invasive methodologies has challenged the invasive method. Non-invasive methods have been initially introduced for chronic hepatitis C with increasing use in other chronic liver diseases. The need for liver biopsy has nowadays decreased significantly as a result of these methodologies. Most of the new non-invasive methods depend on either 'biological' or 'physical' approaches.In this review, starting from the mechanism of fibrogenesis, the current knowledge about diagnosis, treatment strategies and different methods for its evaluation is discussed. This is followed by a conclusion on what is expected to be known in this field during the future research.

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Wnt'er in liver: Expression of Wnt and frizzled genes in mouse

Cited by 132 publications

References 72 publications

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

WNT/β‐catenin signaling in liver health and disease

Liver Fibrosis: Causes and Methods of Assessment, A Review

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