Latexin deficiency in mice up-regulates inflammation and aggravates colitis through HECTD1/Rps3/NF-κB pathway
| Autor: | Guozhang He, Wei Shu, Hua Yang, Yanling Yao, Ming Chen, Zuping Zhou, Taj-Malook Khan, Yaping Li, Shiming Pu, Guangying Qi, Baohua Huang, Xin Liu, Shuang Kan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Ribosomal Proteins
0301 basic medicine Molecular biology Ubiquitin-Protein Ligases lcsh:Medicine Nerve Tissue Proteins Inflammatory bowel disease Article Cell Line Gene Knockout Techniques Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine NF-KappaB Inhibitor alpha Ubiquitin Downregulation and upregulation medicine Animals Humans Amino Acid Sequence Colitis lcsh:Science Inflammation Gene knockdown Multidisciplinary biology Tumor Necrosis Factor-alpha Chemistry lcsh:R NF-kappa B Ubiquitination NF-κB medicine.disease Up-Regulation Ubiquitin ligase IκBα 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Cancer research lcsh:Q Signal Transduction |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The function of Latexin (LXN) in inflammation has attracted attention. However, no data are available regarding its role in colitis. We report that LXN is a suppressor of colitis. LXN deficiency leads to the severity of colitis in DSS-induced mice, and LXN is required for the therapeutic effect of retinoic acid on colitis. Using a proteomics approach, we demonstrate that LXN interacts and forms a functional complex with HECTD1 (an E3 ubiquitin ligase) and ribosomal protein subunit3 (Rps3). IκBα is one of the substrates of HECTD1. Ectopic expression of LXN leads to IκBα accumulation in intestinal epithelial cells, however, LXN knockdown enhances the interaction of HECTD1 and Rps3, contributing to the ubiquitination degradation of IκBα, and subsequently enhances inflammatory response. Thus, our findings provided a novel mechanism underlying LXN modulates colitis via HECTD1/Rps3/NF-κB pathway and significant implications for the development of novel strategies for the treatment of colitis by targeting LXN. |
| Databáze: | OpenAIRE |
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