Pathological Role of Pin1 in the Development of DSS-Induced Colitis
Inflammatory bowel diseases (IBDs) are serious disorders of which the etiologies are not, as yet, fully understood. In this study, Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein was shown to be dramatically upregulated in the colons of dextran sodium sulfate (DSS)-induced ulce...
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MDPI AG
2021-05-01
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| author | Yasuka Matsunaga Shun Hasei Takeshi Yamamotoya Hiroaki Honda Akifumi Kushiyama Hideyuki Sakoda Midori Fujishiro Hiraku Ono Hisanaka Ito Takayoshi Okabe Tomoichiro Asano Yusuke Nakatsu |
| author_facet | Yasuka Matsunaga Shun Hasei Takeshi Yamamotoya Hiroaki Honda Akifumi Kushiyama Hideyuki Sakoda Midori Fujishiro Hiraku Ono Hisanaka Ito Takayoshi Okabe Tomoichiro Asano Yusuke Nakatsu |
| author_sort | Yasuka Matsunaga |
| collection | DOAJ |
| description | Inflammatory bowel diseases (IBDs) are serious disorders of which the etiologies are not, as yet, fully understood. In this study, Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein was shown to be dramatically upregulated in the colons of dextran sodium sulfate (DSS)-induced ulcerative colitis model mice. Interestingly, <i>Pin1</i> knockout (KO) mice exhibited significant attenuation of DSS-induced colitis compared to wild-type (WT) mice, based on various parameters, including body weight, colon length, microscopic observation of the intestinal mucosa, inflammatory cytokine expression, and cleaved caspase-3. In addition, a role of Pin1 in inflammation was suggested because the percentage of M1-type macrophages in the colon was decreased in the <i>Pin1</i> KO mice while that of M2-type macrophages was increased. Moreover, <i>Pin1</i> KO mice showed downregulation of both <i>Il17</i> and <i>Il23a</i> expression in the colon, both of which have been implicated in the development of colitis. Finally, oral administration of Pin1 inhibitor partially but significantly prevented DSS-induced colitis in mice, raising the possibility of Pin1 inhibitors serving as therapeutic agents for IBD. |
| first_indexed | 2024-03-10T11:19:46Z |
| format | Article |
| id | doaj.art-235732759119421e8314cf7b0dc6f10d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:19:46Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-235732759119421e8314cf7b0dc6f10d2023-11-21T20:07:40ZengMDPI AGCells2073-44092021-05-01105123010.3390/cells10051230Pathological Role of Pin1 in the Development of DSS-Induced ColitisYasuka Matsunaga0Shun Hasei1Takeshi Yamamotoya2Hiroaki Honda3Akifumi Kushiyama4Hideyuki Sakoda5Midori Fujishiro6Hiraku Ono7Hisanaka Ito8Takayoshi Okabe9Tomoichiro Asano10Yusuke Nakatsu11Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, JapanDepartment of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, JapanDepartment of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, JapanDepartment of Disease Model, Research Institute of Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, JapanDepartment of Pharmacotherapy, Meiji Pharmaceutical University, Kiyose City, Tokyo 204-8588, JapanDivision of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, JapanDivision of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173-8610, JapanDepartment of Endocrinology, Hematology and Gerontorogy, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, JapanSchool of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDrug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, JapanDepartment of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, JapanInflammatory bowel diseases (IBDs) are serious disorders of which the etiologies are not, as yet, fully understood. In this study, Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) protein was shown to be dramatically upregulated in the colons of dextran sodium sulfate (DSS)-induced ulcerative colitis model mice. Interestingly, <i>Pin1</i> knockout (KO) mice exhibited significant attenuation of DSS-induced colitis compared to wild-type (WT) mice, based on various parameters, including body weight, colon length, microscopic observation of the intestinal mucosa, inflammatory cytokine expression, and cleaved caspase-3. In addition, a role of Pin1 in inflammation was suggested because the percentage of M1-type macrophages in the colon was decreased in the <i>Pin1</i> KO mice while that of M2-type macrophages was increased. Moreover, <i>Pin1</i> KO mice showed downregulation of both <i>Il17</i> and <i>Il23a</i> expression in the colon, both of which have been implicated in the development of colitis. Finally, oral administration of Pin1 inhibitor partially but significantly prevented DSS-induced colitis in mice, raising the possibility of Pin1 inhibitors serving as therapeutic agents for IBD.https://www.mdpi.com/2073-4409/10/5/1230Pin1ulcerative colitisdextran sodium sulfatePin1 inhibitorknockout mice |
| spellingShingle | Yasuka Matsunaga Shun Hasei Takeshi Yamamotoya Hiroaki Honda Akifumi Kushiyama Hideyuki Sakoda Midori Fujishiro Hiraku Ono Hisanaka Ito Takayoshi Okabe Tomoichiro Asano Yusuke Nakatsu Pathological Role of Pin1 in the Development of DSS-Induced Colitis Cells Pin1 ulcerative colitis dextran sodium sulfate Pin1 inhibitor knockout mice |
| title | Pathological Role of Pin1 in the Development of DSS-Induced Colitis |
| title_full | Pathological Role of Pin1 in the Development of DSS-Induced Colitis |
| title_fullStr | Pathological Role of Pin1 in the Development of DSS-Induced Colitis |
| title_full_unstemmed | Pathological Role of Pin1 in the Development of DSS-Induced Colitis |
| title_short | Pathological Role of Pin1 in the Development of DSS-Induced Colitis |
| title_sort | pathological role of pin1 in the development of dss induced colitis |
| topic | Pin1 ulcerative colitis dextran sodium sulfate Pin1 inhibitor knockout mice |
| url | https://www.mdpi.com/2073-4409/10/5/1230 |
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