Dataset Information

MiR-155 promotes colitis-associated intestinal fibrosis by targeting HBP1/Wnt/β-catenin signalling pathway.

ABSTRACT: Intestinal fibrosis is the most common complication of Crohn's disease (CD) that is one major disorder of inflammatory bowel disease (IBD), but the precise mechanism remains unclear. MiR-155 has been involved in fibrotic diseases. Here, we determined the role of miR-155 in regulating intestinal fibrosis. MiR-155 levels were significantly up-regulated in CD patients with intestinal stricture CD. The overexpression of miR-155 significantly aggravated TNBS-induced CD-associated intestinal fibrosis. Mechanistically, we identified that HBP1, a negative regulator of the Wnt/β-catenin signalling pathway, is a direct target of miR-155. Moreover, in vitro and in vivo experiments suggested that the miR-155/HBP1 axis activates Wnt/β-catenin signalling pathway to induce intestinal fibrosis. Taken together, we demonstrated that miR-155 directly targets HBP1 to induce CD-associated intestinal fibrosis via Wnt/β-catenin signalling pathway.

SUBMITTER: Li N

PROVIDER: S-EPMC8107084 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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MiR-155 promotes colitis-associated intestinal fibrosis by targeting HBP1/Wnt/β-catenin signalling pathway.

Li Nianshuang N Ouyang Yaobin Y Xu Xinbo X Yuan Zhenxiang Z Liu Chunquan C Zhu Zhenhua Z

Journal of cellular and molecular medicine 20210326 10

Intestinal fibrosis is the most common complication of Crohn's disease (CD) that is one major disorder of inflammatory bowel disease (IBD), but the precise mechanism remains unclear. MiR-155 has been involved in fibrotic diseases. Here, we determined the role of miR-155 in regulating intestinal fibrosis. MiR-155 levels were significantly up-regulated in CD patients with intestinal stricture CD. The overexpression of miR-155 significantly aggravated TNBS-induced CD-associated intestinal fibrosis. ...[more]

PMID: 33769664

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Project description:Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors. As a result of their acylation, Wnt proteins are very hydrophobic and require detergents for purification, which presents major obstacles to the preparation and application of recombinant Wnt proteins. This hydrophobicity has hindered the determination of the molecular mechanisms of Wnt signalling activation and the functional importance of FZD subtypes, and the use of Wnt proteins as therapeutic agents. Here we develop surrogate Wnt agonists, water-soluble FZD-LRP5/LRP6 heterodimerizers, with FZD5/FZD8-specific and broadly FZD-reactive binding domains. Similar to WNT3A, these Wnt agonists elicit a characteristic β-catenin signalling response in a FZD-selective fashion, enhance the osteogenic lineage commitment of primary mouse and human mesenchymal stem cells, and support the growth of a broad range of primary human organoid cultures. In addition, the surrogates can be systemically expressed and exhibit Wnt activity in vivo in the mouse liver, regulating metabolic liver zonation and promoting hepatocyte proliferation, resulting in hepatomegaly. These surrogates demonstrate that canonical Wnt signalling can be activated by bi-specific ligands that induce receptor heterodimerization. Furthermore, these easily produced, non-lipidated Wnt surrogate agonists facilitate functional studies of Wnt signalling and the exploration of Wnt agonists for translational applications in regenerative medicine.

Dataset Information

MiR-155 promotes colitis-associated intestinal fibrosis by targeting HBP1/Wnt/β-catenin signalling pathway.

Publications

MiR-155 promotes colitis-associated intestinal fibrosis by targeting HBP1/Wnt/β-catenin signalling pathway.

Similar Datasets

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