Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α.
Pancreatic β-cell failure is a pathological feature in type 1 diabetes. One promising approach involves inducing transdifferentiation of related pancreatic cell types, specifically α cells that produce glucagon. The chemokine stromal cell-derived factor-1 alpha (SDF-1α) is implicated in pancreatic α...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0299821&type=printable |
| _version_ | 1827572358345392128 |
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| author | Hongmei Lang Ning Lin Xiaorong Chen Jie Xiang Xingping Zhang Chao Kang |
| author_facet | Hongmei Lang Ning Lin Xiaorong Chen Jie Xiang Xingping Zhang Chao Kang |
| author_sort | Hongmei Lang |
| collection | DOAJ |
| description | Pancreatic β-cell failure is a pathological feature in type 1 diabetes. One promising approach involves inducing transdifferentiation of related pancreatic cell types, specifically α cells that produce glucagon. The chemokine stromal cell-derived factor-1 alpha (SDF-1α) is implicated in pancreatic α-to-β like cell transition. Here, the serum level of SDF-1α was lower in T1D with C-peptide loss, the miR-23a was negatively correlated with SDF-1α. We discovered that exosomal miR-23a, secreted from β cells, functionally downregulates the expression of SDF-1α, leading to increased Pax4 expression and decreased Arx expression in vivo. Adenovirus-vectored miR-23a sponge and mimic were constructed to further explored the miR-23a on pancreatic α-to-β like cell transition in vitro, which yielded results consistent with our cell-based assays. Suppression of miR-23a upregulated insulin level and downregulated glucagon level in STZ-induced diabetes mice models, effectively promoting α-to-β like cell transition. Our findings highlight miR-23a as a new therapeutic target for regenerating pancreatic β cells from α cells. |
| first_indexed | 2024-04-24T16:29:43Z |
| format | Article |
| id | doaj.art-c7a7d14211e84b548df6726d6a8f3632 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-24T16:29:43Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c7a7d14211e84b548df6726d6a8f36322024-03-30T05:33:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01193e029982110.1371/journal.pone.0299821Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α.Hongmei LangNing LinXiaorong ChenJie XiangXingping ZhangChao KangPancreatic β-cell failure is a pathological feature in type 1 diabetes. One promising approach involves inducing transdifferentiation of related pancreatic cell types, specifically α cells that produce glucagon. The chemokine stromal cell-derived factor-1 alpha (SDF-1α) is implicated in pancreatic α-to-β like cell transition. Here, the serum level of SDF-1α was lower in T1D with C-peptide loss, the miR-23a was negatively correlated with SDF-1α. We discovered that exosomal miR-23a, secreted from β cells, functionally downregulates the expression of SDF-1α, leading to increased Pax4 expression and decreased Arx expression in vivo. Adenovirus-vectored miR-23a sponge and mimic were constructed to further explored the miR-23a on pancreatic α-to-β like cell transition in vitro, which yielded results consistent with our cell-based assays. Suppression of miR-23a upregulated insulin level and downregulated glucagon level in STZ-induced diabetes mice models, effectively promoting α-to-β like cell transition. Our findings highlight miR-23a as a new therapeutic target for regenerating pancreatic β cells from α cells.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0299821&type=printable |
| spellingShingle | Hongmei Lang Ning Lin Xiaorong Chen Jie Xiang Xingping Zhang Chao Kang Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α. PLoS ONE |
| title | Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α. |
| title_full | Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α. |
| title_fullStr | Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α. |
| title_full_unstemmed | Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α. |
| title_short | Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α. |
| title_sort | repressing mir 23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of sdf 1α |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0299821&type=printable |
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