Reduced chondroitin sulfate content prevents diabetic neuropathy through transforming growth factor-β signaling suppression.
Autor: | Ishiguro H; Departments of Hematology, Endocrinology, and Metabolism, Graduate School of Medical and Dental Sciences, Niigata university, Niigata, Japan., Ushiki T; Departments of Hematology, Endocrinology, and Metabolism, Graduate School of Medical and Dental Sciences, Niigata university, Niigata, Japan.; Division of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan.; Departments of Transfusion Medicine, Cell Therapy and Regenerative Medicine, Medical and Dental Hospital, Niigata University, Niigata, Japan., Honda A; Department of Neurochemistry and Molecular Cell Biology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.; Center for Research Promotion, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan., Yoshimatsu Y; Division of Pharmacology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan., Ohashi R; Divisions of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan., Okuda S; Division of Bioinformatics, Graduate School of Medical and Dental Sciences, Niigata, Japan., Kawasaki A; Department of Neurochemistry and Molecular Cell Biology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan., Cho K; Departments of Hematology, Endocrinology, and Metabolism, Graduate School of Medical and Dental Sciences, Niigata university, Niigata, Japan., Tamura S; Departments of Hematology, Endocrinology, and Metabolism, Graduate School of Medical and Dental Sciences, Niigata university, Niigata, Japan., Suwabe T; Departments of Hematology, Endocrinology, and Metabolism, Graduate School of Medical and Dental Sciences, Niigata university, Niigata, Japan., Katagiri T; Departments of Hematology, Endocrinology, and Metabolism, Graduate School of Medical and Dental Sciences, Niigata university, Niigata, Japan., Ling Y; Division of Bioinformatics, Graduate School of Medical and Dental Sciences, Niigata, Japan., Iijima A; Neurophysiology & Biomedical Engineering Lab, Interdisciplinary Program of Biomedical Engineering, Assistive Technology and Art and Sports Sciences, Faculty of Engineering, Niigata University Niigata, Niigata, Japan., Mikami T; Laboratory of Biochemistry, Kobe Pharmaceutical University, Kobe, Japan., Kitagawa H; Laboratory of Biochemistry, Kobe Pharmaceutical University, Kobe, Japan., Uemura A; Department of Retinal Vascular Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan., Sango K; Diabetic Neuropathy Project, Department of Diseases and Infection, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan., Masuko M; Departments of Hematology, Endocrinology, and Metabolism, Graduate School of Medical and Dental Sciences, Niigata university, Niigata, Japan.; Hematopoietic Cell Transplantation Niigata University Medical and Dental Hospital, , Niigata University, Niigata, Japan., Igarashi M; Department of Neurochemistry and Molecular Cell Biology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan., Sone H; Departments of Hematology, Endocrinology, and Metabolism, Graduate School of Medical and Dental Sciences, Niigata university, Niigata, Japan. |
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Jazyk: | angličtina |
Zdroj: | IScience [iScience] 2024 Mar 18; Vol. 27 (4), pp. 109528. Date of Electronic Publication: 2024 Mar 18 (Print Publication: 2024). |
DOI: | 10.1016/j.isci.2024.109528 |
Abstrakt: | Diabetic neuropathy (DN) is a major complication of diabetes mellitus . Chondroitin sulfate (CS) is one of the most important extracellular matrix components and is known to interact with various diffusible factors; however, its role in DN pathology has not been examined. Therefore, we generated CSGalNAc-T1 knockout (T1KO) mice, in which CS levels were reduced. We demonstrated that diabetic T1KO mice were much more resistant to DN than diabetic wild-type (WT) mice. We also found that interactions between pericytes and vascular endothelial cells were more stable in T1KO mice. Among the RNA-seq results, we focused on the transforming growth factor β signaling pathway and found that the phosphorylation of Smad2/3 was less upregulated in T1KO mice than in WT mice under hyperglycemic conditions. Taken together, a reduction in CS level attenuates DN progression, indicating that CS is an important factor in DN pathogenesis. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).) |
Databáze: | MEDLINE |
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