Claudin 4 in pancreatic β cells is involved in regulating the functional state of adult islets
| Autor: | Hongtu Li, Takahiro Nagatake, Fang-Xu Jiang, Abraham Neelankal John, Yoko Hamazaki |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
bioinformatics analysis endocrine system endocrine system diseases claudin 4 Enteroendocrine cell Biology Incretins General Biochemistry Genetics and Molecular Biology Islets of Langerhans Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Insulin Claudin-4 Claudin lcsh:QH301-705.5 Transcription factor Research Articles Cells Cultured Mice Knockout geography geography.geographical_feature_category Tight junction functional state Pancreatic islets dedifferentiation Structural gene Computational Biology Glucose Tolerance Test β cells Islet Cell biology Glucose 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) 030220 oncology & carcinogenesis Pancreas Research Article |
| Zdroj: | FEBS Open Bio FEBS Open Bio, Vol 10, Iss 1, Pp 28-40 (2020) |
| ISSN: | 2211-5463 |
| DOI: | 10.1002/2211-5463.12735 |
| Popis: | 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. Claudin 4 (Cldn4) is developmentally up‐regulated in developing pancreatic islet cells, is involved in sustaining the functional state (FS) in mature islets and is pathologically down‐regulated to compromise the FS in diabetic β cells. |
| Databáze: | OpenAIRE |
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