Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus
Skeletal muscle wasting in patients with diabetes mellitus (DM) is a complication of decreased muscle mass and strength, and is a serious risk factor that may result in mortality. Deteriorated differentiation of muscle precursor cells, called myoblasts, in DM patients is considered to be one of the...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.679152/full |
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| author | Shunichi Nakamura Shinichi Yonekura Shinichi Yonekura Takeshi Shimosato Takeshi Shimosato Takeshi Shimosato Tomohide Takaya Tomohide Takaya Tomohide Takaya |
| author_facet | Shunichi Nakamura Shinichi Yonekura Shinichi Yonekura Takeshi Shimosato Takeshi Shimosato Takeshi Shimosato Tomohide Takaya Tomohide Takaya Tomohide Takaya |
| author_sort | Shunichi Nakamura |
| collection | DOAJ |
| description | Skeletal muscle wasting in patients with diabetes mellitus (DM) is a complication of decreased muscle mass and strength, and is a serious risk factor that may result in mortality. Deteriorated differentiation of muscle precursor cells, called myoblasts, in DM patients is considered to be one of the causes of muscle wasting. We recently developed myogenetic oligodeoxynucleotides (myoDNs), which are 18-base single-strand DNAs that promote myoblast differentiation by targeting nucleolin. Herein, we report the applicability of a myoDN, iSN04, to myoblasts isolated from patients with type 1 and type 2 DM. Myogenesis of DM myoblasts was exacerbated concordantly with a delayed shift of myogenic transcription and induction of interleukins. Analogous phenotypes were reproduced in healthy myoblasts cultured with excessive glucose or palmitic acid, mimicking hyperglycemia or hyperlipidemia. iSN04 treatment recovered the deteriorated differentiation of plural DM myoblasts by downregulating myostatin and interleukin-8 (IL-8). iSN04 also ameliorated the impaired myogenic differentiation induced by glucose or palmitic acid. These results demonstrate that myoDNs can directly facilitate myoblast differentiation in DM patients, making them novel candidates for nucleic acid drugs to treat muscle wasting in patients with DM. |
| first_indexed | 2024-12-21T22:20:04Z |
| format | Article |
| id | doaj.art-e05a08e193f34236a3e14ab3fd4ca334 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-21T22:20:04Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-e05a08e193f34236a3e14ab3fd4ca3342022-12-21T18:48:21ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-05-011210.3389/fphys.2021.679152679152Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes MellitusShunichi Nakamura0Shinichi Yonekura1Shinichi Yonekura2Takeshi Shimosato3Takeshi Shimosato4Takeshi Shimosato5Tomohide Takaya6Tomohide Takaya7Tomohide Takaya8Department of Agriculture, Graduate School of Science and Technology, Shinshu University, Nagano, JapanDepartment of Agricultural and Life Sciences, Faculty of Agriculture, Shinshu University, Nagano, JapanDepartment of Biomolecular Innovation, Institute for Biomedical Sciences, Shinshu University, Nagano, JapanDepartment of Agriculture, Graduate School of Science and Technology, Shinshu University, Nagano, JapanDepartment of Agricultural and Life Sciences, Faculty of Agriculture, Shinshu University, Nagano, JapanDepartment of Biomolecular Innovation, Institute for Biomedical Sciences, Shinshu University, Nagano, JapanDepartment of Agriculture, Graduate School of Science and Technology, Shinshu University, Nagano, JapanDepartment of Agricultural and Life Sciences, Faculty of Agriculture, Shinshu University, Nagano, JapanDepartment of Biomolecular Innovation, Institute for Biomedical Sciences, Shinshu University, Nagano, JapanSkeletal muscle wasting in patients with diabetes mellitus (DM) is a complication of decreased muscle mass and strength, and is a serious risk factor that may result in mortality. Deteriorated differentiation of muscle precursor cells, called myoblasts, in DM patients is considered to be one of the causes of muscle wasting. We recently developed myogenetic oligodeoxynucleotides (myoDNs), which are 18-base single-strand DNAs that promote myoblast differentiation by targeting nucleolin. Herein, we report the applicability of a myoDN, iSN04, to myoblasts isolated from patients with type 1 and type 2 DM. Myogenesis of DM myoblasts was exacerbated concordantly with a delayed shift of myogenic transcription and induction of interleukins. Analogous phenotypes were reproduced in healthy myoblasts cultured with excessive glucose or palmitic acid, mimicking hyperglycemia or hyperlipidemia. iSN04 treatment recovered the deteriorated differentiation of plural DM myoblasts by downregulating myostatin and interleukin-8 (IL-8). iSN04 also ameliorated the impaired myogenic differentiation induced by glucose or palmitic acid. These results demonstrate that myoDNs can directly facilitate myoblast differentiation in DM patients, making them novel candidates for nucleic acid drugs to treat muscle wasting in patients with DM.https://www.frontiersin.org/articles/10.3389/fphys.2021.679152/fullmyogenetic oligodeoxynucleotideskeletal musclemyoblastmyogenic differentiationdiabetes mellitus |
| spellingShingle | Shunichi Nakamura Shinichi Yonekura Shinichi Yonekura Takeshi Shimosato Takeshi Shimosato Takeshi Shimosato Tomohide Takaya Tomohide Takaya Tomohide Takaya Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus Frontiers in Physiology myogenetic oligodeoxynucleotide skeletal muscle myoblast myogenic differentiation diabetes mellitus |
| title | Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus |
| title_full | Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus |
| title_fullStr | Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus |
| title_full_unstemmed | Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus |
| title_short | Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus |
| title_sort | myogenetic oligodeoxynucleotide myodn recovers the differentiation of skeletal muscle myoblasts deteriorated by diabetes mellitus |
| topic | myogenetic oligodeoxynucleotide skeletal muscle myoblast myogenic differentiation diabetes mellitus |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.679152/full |
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