Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets
The functional state (FS) of adult pancreatic islets is regulated by a large array of regulatory molecules including numerous transcription factors. Whether any islet structural molecules play such a role has not been well understood. Here, multiple technologies including bioinformatics analyses wer...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12735 |
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| author | Hongtu Li Abraham Neelankal John Takahiro Nagatake Yoko Hamazaki Fang‐Xu Jiang |
| author_facet | Hongtu Li Abraham Neelankal John Takahiro Nagatake Yoko Hamazaki Fang‐Xu Jiang |
| author_sort | Hongtu Li |
| collection | DOAJ |
| description | The functional state (FS) of adult pancreatic islets is regulated by a large array of regulatory molecules including numerous transcription factors. Whether any islet structural molecules play such a role has not been well understood. Here, multiple technologies including bioinformatics analyses were used to explore such molecules. The tight junction family molecule claudin 4 (Cldn4) was the highest enriched amongst over 140 structural genes analysed. Cldn4 expression was ~75‐fold higher in adult islets than in exocrine tissues and was mostly up‐regulated during functional maturation of developing islet cells. Cldn4 was progressively down‐regulated in functionally compromised, dedifferentiating insulin‐secreting β cells and in db/db type 2 diabetic islets. Furthermore, the genetic deletion of Cldn4 impaired significantly the FS without apparently affecting pancreas morphology, islet architectural structure and cellular distribution, and secretion of enteroendocrine hormones. Thus, we suggest a previously unidentified role for Cldn4 in regulating the FS of islets, with implications in translational research for better diabetes therapies. |
| format | Article |
| id | doaj-art-37eb1df581bd45cfb92a11e63c42ebca |
| institution | OA Journals |
| issn | 2211-5463 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-37eb1df581bd45cfb92a11e63c42ebca2025-08-20T01:54:33ZengWileyFEBS Open Bio2211-54632020-01-01101284010.1002/2211-5463.12735Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult isletsHongtu Li0Abraham Neelankal John1Takahiro Nagatake2Yoko Hamazaki3Fang‐Xu Jiang4Islet Cell Development Program Faculty of Medical Science Harry Perkins Institute of Medical Research University of Western Australia Nedlands WA AustraliaIslet Cell Development Program Faculty of Medical Science Harry Perkins Institute of Medical Research University of Western Australia Nedlands WA AustraliaDepartment of Immunology and Cell Biology Graduate School of Medicine Kyoto University JapanDepartment of Immunology and Cell Biology Graduate School of Medicine Kyoto University JapanIslet Cell Development Program Faculty of Medical Science Harry Perkins Institute of Medical Research University of Western Australia Nedlands WA AustraliaThe functional state (FS) of adult pancreatic islets is regulated by a large array of regulatory molecules including numerous transcription factors. Whether any islet structural molecules play such a role has not been well understood. Here, multiple technologies including bioinformatics analyses were used to explore such molecules. The tight junction family molecule claudin 4 (Cldn4) was the highest enriched amongst over 140 structural genes analysed. Cldn4 expression was ~75‐fold higher in adult islets than in exocrine tissues and was mostly up‐regulated during functional maturation of developing islet cells. Cldn4 was progressively down‐regulated in functionally compromised, dedifferentiating insulin‐secreting β cells and in db/db type 2 diabetic islets. Furthermore, the genetic deletion of Cldn4 impaired significantly the FS without apparently affecting pancreas morphology, islet architectural structure and cellular distribution, and secretion of enteroendocrine hormones. Thus, we suggest a previously unidentified role for Cldn4 in regulating the FS of islets, with implications in translational research for better diabetes therapies.https://doi.org/10.1002/2211-5463.12735β cellsbioinformatics analysisclaudin 4dedifferentiationfunctional state |
| spellingShingle | Hongtu Li Abraham Neelankal John Takahiro Nagatake Yoko Hamazaki Fang‐Xu Jiang Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets FEBS Open Bio β cells bioinformatics analysis claudin 4 dedifferentiation functional state |
| title | Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets |
| title_full | Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets |
| title_fullStr | Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets |
| title_full_unstemmed | Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets |
| title_short | Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets |
| title_sort | claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets |
| topic | β cells bioinformatics analysis claudin 4 dedifferentiation functional state |
| url | https://doi.org/10.1002/2211-5463.12735 |
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