The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner
Summary: The matricellular protein Fibulin-5 (Fbln5) is a secreted protein that is essential for elastic fiber formation, and pancreatic islets are usually surrounded by the extracellular matrix (ECM), which includes elastic fibers. However, much uncertainty remains regarding the function of the ECM...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001166 |
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| author | Tomoko Okuyama Takahiro Tsuno Ryota Inoue Setsuko Fukushima Mayu Kyohara Anzu Matsumura Daisuke Miyashita Kuniyuki Nishiyama Yusuke Takano Yu Togashi Makiko Meguro-Horike Shin-ichi Horike Tatsuya Kin A.M. James Shapiro Hiromi Yanagisawa Yasuo Terauchi Jun Shirakawa |
| author_facet | Tomoko Okuyama Takahiro Tsuno Ryota Inoue Setsuko Fukushima Mayu Kyohara Anzu Matsumura Daisuke Miyashita Kuniyuki Nishiyama Yusuke Takano Yu Togashi Makiko Meguro-Horike Shin-ichi Horike Tatsuya Kin A.M. James Shapiro Hiromi Yanagisawa Yasuo Terauchi Jun Shirakawa |
| author_sort | Tomoko Okuyama |
| collection | DOAJ |
| description | Summary: The matricellular protein Fibulin-5 (Fbln5) is a secreted protein that is essential for elastic fiber formation, and pancreatic islets are usually surrounded by the extracellular matrix (ECM), which includes elastic fibers. However, much uncertainty remains regarding the function of the ECM and its components in β-cells. Here, we describe the role of Fbln5 in β-cell replication. Fbln5 expression was increased upon glucose stimulation in β-cells of mouse and human islets. β-Cell-specific Fbln5-knockout (βFbln5KO) mice exhibit significantly reduced β-cell proliferation in vivo but not in vitro. Secreted extracellular Fbln5 enhances β-cell replication. Fbln5-deficient β-cells exhibit the downregulated expression of the gene encoding Polo-like kinase 1 (PLK1), which is accompanied by ERK-mediated FoxM1 nuclear export. These data suggest that Fbln5 is secreted from β-cells in response to glucose and plays important roles in the appropriate maintenance of β-cell functions in an autocrine or paracrine manner. |
| format | Article |
| id | doaj-art-361baf79135d44009086e14e2e271600 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-361baf79135d44009086e14e2e2716002025-02-08T05:00:49ZengElsevieriScience2589-00422025-02-01282111856The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine mannerTomoko Okuyama0Takahiro Tsuno1Ryota Inoue2Setsuko Fukushima3Mayu Kyohara4Anzu Matsumura5Daisuke Miyashita6Kuniyuki Nishiyama7Yusuke Takano8Yu Togashi9Makiko Meguro-Horike10Shin-ichi Horike11Tatsuya Kin12A.M. James Shapiro13Hiromi Yanagisawa14Yasuo Terauchi15Jun Shirakawa16Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, JapanDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan; Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, JapanDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan; Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, JapanLaboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, JapanDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, JapanLaboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, JapanDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, JapanDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan; Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, JapanDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, JapanDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, JapanResearch Center for Experimental Modeling of Human Disease, Kanazawa University, Kanazawa, JapanResearch Center for Experimental Modeling of Human Disease, Kanazawa University, Kanazawa, JapanClinical Islet Laboratory and Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, CanadaClinical Islet Laboratory and Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, CanadaLife Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, JapanDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, JapanDepartment of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan; Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, Japan; Corresponding authorSummary: The matricellular protein Fibulin-5 (Fbln5) is a secreted protein that is essential for elastic fiber formation, and pancreatic islets are usually surrounded by the extracellular matrix (ECM), which includes elastic fibers. However, much uncertainty remains regarding the function of the ECM and its components in β-cells. Here, we describe the role of Fbln5 in β-cell replication. Fbln5 expression was increased upon glucose stimulation in β-cells of mouse and human islets. β-Cell-specific Fbln5-knockout (βFbln5KO) mice exhibit significantly reduced β-cell proliferation in vivo but not in vitro. Secreted extracellular Fbln5 enhances β-cell replication. Fbln5-deficient β-cells exhibit the downregulated expression of the gene encoding Polo-like kinase 1 (PLK1), which is accompanied by ERK-mediated FoxM1 nuclear export. These data suggest that Fbln5 is secreted from β-cells in response to glucose and plays important roles in the appropriate maintenance of β-cell functions in an autocrine or paracrine manner.http://www.sciencedirect.com/science/article/pii/S2589004225001166Cell biologyFunctional aspects of cell biology |
| spellingShingle | Tomoko Okuyama Takahiro Tsuno Ryota Inoue Setsuko Fukushima Mayu Kyohara Anzu Matsumura Daisuke Miyashita Kuniyuki Nishiyama Yusuke Takano Yu Togashi Makiko Meguro-Horike Shin-ichi Horike Tatsuya Kin A.M. James Shapiro Hiromi Yanagisawa Yasuo Terauchi Jun Shirakawa The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner iScience Cell biology Functional aspects of cell biology |
| title | The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner |
| title_full | The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner |
| title_fullStr | The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner |
| title_full_unstemmed | The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner |
| title_short | The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner |
| title_sort | matricellular protein fibulin 5 regulates β cell proliferation in an autocrine paracrine manner |
| topic | Cell biology Functional aspects of cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001166 |
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