Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6
Hyaluronan (HA) has proven to be beneficial in the treatment of several diseases. Recently, it has been shown that the local application of HA (IBD98E) improves endoscopic and clinical outcomes in subjects with active distal ulcerative colitis (UC). However, the mechanisms by which this polysacchari...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/9/1074 |
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| author | Giusy Sammarco Mohammad Shalaby Sudharshan Elangovan Luciana Petti Giulia Roda Silvia Restelli Vincenzo Arena Federica Ungaro Gionata Fiorino Anthony J. Day Silvia D’Alessio Stefania Vetrano |
| author_facet | Giusy Sammarco Mohammad Shalaby Sudharshan Elangovan Luciana Petti Giulia Roda Silvia Restelli Vincenzo Arena Federica Ungaro Gionata Fiorino Anthony J. Day Silvia D’Alessio Stefania Vetrano |
| author_sort | Giusy Sammarco |
| collection | DOAJ |
| description | Hyaluronan (HA) has proven to be beneficial in the treatment of several diseases. Recently, it has been shown that the local application of HA (IBD98E) improves endoscopic and clinical outcomes in subjects with active distal ulcerative colitis (UC). However, the mechanisms by which this polysaccharide exerts its beneficial effects are unclear. Here, we demonstrated that HA treatment in vitro and in vivo improved mucosal healing by accelerating intestinal epithelial regeneration. Indeed, mice treated with HA showed a faster recovery from colitis and reduced endoscopic signs of mucosal inflammation compared to those receiving saline. Furthermore, histological analysis revealed less ulcerated mucosa in mice treated with HA, characterized by re-epithelialized areas. TSG-6, the secreted product of TNF-stimulated gene-6, is an HA-binding protein shown previously to have tissue-protective properties and promote wound healing. Mucosal levels of TSG-6 increased in UC patients compared to the healthy controls and also after wounding in mice. TSG-6 deletion prevented the beneficial properties of HA in mucosal wound repair, suggesting that the interaction of HA with TSG-6 is crucial for intestinal epithelial regeneration. Overall these results are consistent with HA having a therapeutic effect via the promotion of mucosal healing in patients with ulcerative colitis. |
| first_indexed | 2024-03-12T19:54:48Z |
| format | Article |
| id | doaj.art-c19b8ca9735b4dfe874f184474c595d1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:54:48Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c19b8ca9735b4dfe874f184474c595d12023-08-02T02:54:08ZengMDPI AGCells2073-44092019-09-0189107410.3390/cells8091074cells8091074Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6Giusy Sammarco0Mohammad Shalaby1Sudharshan Elangovan2Luciana Petti3Giulia Roda4Silvia Restelli5Vincenzo Arena6Federica Ungaro7Gionata Fiorino8Anthony J. Day9Silvia D’Alessio10Stefania Vetrano11IBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, ItalyIBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, ItalyGenomics Division, Wipro Life Sciences laboratory, WIPRO Limited, Bengaluru 560035, Karnataka, IndiaIBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, ItalyIBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, ItalyIBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, ItalyArea of Pathology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00147 Rome, ItalyIBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, ItalyDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, ItalyWellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine, & Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKIBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, ItalyIBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, ItalyHyaluronan (HA) has proven to be beneficial in the treatment of several diseases. Recently, it has been shown that the local application of HA (IBD98E) improves endoscopic and clinical outcomes in subjects with active distal ulcerative colitis (UC). However, the mechanisms by which this polysaccharide exerts its beneficial effects are unclear. Here, we demonstrated that HA treatment in vitro and in vivo improved mucosal healing by accelerating intestinal epithelial regeneration. Indeed, mice treated with HA showed a faster recovery from colitis and reduced endoscopic signs of mucosal inflammation compared to those receiving saline. Furthermore, histological analysis revealed less ulcerated mucosa in mice treated with HA, characterized by re-epithelialized areas. TSG-6, the secreted product of TNF-stimulated gene-6, is an HA-binding protein shown previously to have tissue-protective properties and promote wound healing. Mucosal levels of TSG-6 increased in UC patients compared to the healthy controls and also after wounding in mice. TSG-6 deletion prevented the beneficial properties of HA in mucosal wound repair, suggesting that the interaction of HA with TSG-6 is crucial for intestinal epithelial regeneration. Overall these results are consistent with HA having a therapeutic effect via the promotion of mucosal healing in patients with ulcerative colitis.https://www.mdpi.com/2073-4409/8/9/1074mucosal healingepithelial regenerationTSG-6inflammatory bowel diseaseexperimental colitishyaluronan |
| spellingShingle | Giusy Sammarco Mohammad Shalaby Sudharshan Elangovan Luciana Petti Giulia Roda Silvia Restelli Vincenzo Arena Federica Ungaro Gionata Fiorino Anthony J. Day Silvia D’Alessio Stefania Vetrano Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6 Cells mucosal healing epithelial regeneration TSG-6 inflammatory bowel disease experimental colitis hyaluronan |
| title | Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6 |
| title_full | Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6 |
| title_fullStr | Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6 |
| title_full_unstemmed | Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6 |
| title_short | Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6 |
| title_sort | hyaluronan accelerates intestinal mucosal healing through interaction with tsg 6 |
| topic | mucosal healing epithelial regeneration TSG-6 inflammatory bowel disease experimental colitis hyaluronan |
| url | https://www.mdpi.com/2073-4409/8/9/1074 |
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