The Insect Peptide CopA3 Increases Colonic Epithelial Cell Proliferation and Mucosal Barrier Function to Prevent Inflammatory Responses in the Gut
| Autor: | Dae Hong Kim, Peng Zhang, Charalabos Pothoulakis, Ik Hwan Lee, Ho Kim, Li Fang Lu, Junguee Lee, Jae Sam Hwang, Seung Taek Nam, Ji Hong, John T. LaMont, Heon Seok |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Anti-Inflammatory Agents Small Inbred C57BL Biochemistry Medical and Health Sciences epidermal growth factor (EGF) Tissue Culture Techniques Mice 0302 clinical medicine Intestinal mucosa Beetles Intestine Small ubiquitylation (ubiquitination) Intestinal Mucosa Barrier function Gastrointestinal agent Anti-Inflammatory Agents Non-Steroidal Molecular Bases of Disease Cell cycle Biological Sciences Colitis Enteritis Cell biology Intestine Coleoptera epidermal growth factor 030220 oncology & carcinogenesis protein degradation Insect Proteins RNA Interference cell cycle medicine.symptom Non-Steroidal HT29 Cells Cyclin-Dependent Kinase Inhibitor p21 Biochemistry & Molecular Biology Colon Ubiquitin-Protein Ligases Inflammation Protein degradation Biology Permeability 03 medical and health sciences Gastrointestinal Agents Animals Outbred Strains medicine Animals Humans bacterial toxin ubiquitylation Molecular Biology Cell Proliferation Cell growth epithelial cell Ubiquitination Cell Biology medicine.disease Mice Inbred C57BL 030104 developmental biology cell proliferation proteasome Outbred Strains inflammation Immunology Chemical Sciences peptides Antimicrobial Cationic Peptides |
| Zdroj: | Kim, DH; Hwang, JS; Lee, IH; Nam, ST; Hong, J; Zhang, P; et al.(2016). The Insect Peptide CopA3 Increases Colonic Epithelial Cell Proliferation and Mucosal Barrier Function to Prevent Inflammatory Responses in the Gut. JOURNAL OF BIOLOGICAL CHEMISTRY, 291(7), 3209-3223. doi: 10.1074/jbc.M115.682856. UCLA: Retrieved from: http://www.escholarship.org/uc/item/5vq012bb The Journal of biological chemistry, vol 291, iss 7 |
| DOI: | 10.1074/jbc.M115.682856. |
| Popis: | The epithelial cells of the gut form a physical barrier against the luminal contents. The collapse of this barrier causes inflammation, and its therapeutic restoration can protect the gut against inflammation. EGF enhances mucosal barrier function and increases colonocyte proliferation, thereby ameliorating inflammatory responses in the gut. Based on our previous finding that the insect peptide CopA3 promotes neuronal growth, we herein tested whether CopA3 could increase the cell proliferation of colonocytes, enhance mucosal barrier function, and ameliorate gut inflammation. Our results revealed that CopA3 significantly increased epithelial cell proliferation in mouse colonic crypts and also enhanced colonic epithelial barrier function. Moreover, CopA3 treatment ameliorated Clostridium difficile toxin As-induced inflammation responses in the mouse small intestine (acute enteritis) and completely blocked inflammatory responses and subsequent lethality in the dextran sulfate sodium-induced mouse model of chronic colitis. The marked CopA3-induced increase of colonocyte proliferation was found to require rapid protein degradation of p21(Cip1/Waf1), and an in vitro ubiquitination assay revealed that CopA3 directly facilitated ubiquitin ligase activity against p21(Cip1/Waf1). Taken together, our findings indicate that the insect peptide CopA3 prevents gut inflammation by increasing epithelial cell proliferation and mucosal barrier function. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|