Reduced chondroitin sulfate content prevents diabetic neuropathy through transforming growth factor-β signaling suppression

• DOI: 10.1016/j.isci.2024.109528
• Publication Date: 2024-03-18T16:31:30Z
• Authors: Hajime Ishiguro; Takashi Ushiki; Atsuko Honda; Yasuhiro Yoshimatsu; Riuko Ohashi; Shujiro Okuda; Asami Kawasaki; Kaori Cho; Suguru Tamura; Tatsuya Suwabe; Takayuki Katagiri; Yiwei Ling; Atsuhiko Iijima; Tadahisa Mikami; Hiroshi Kitagawa; Akiyoshi Uemura; Kazunori Sango; Masayoshi Masuko; Michihiro Igarashi; Hirohito Sone
• Keywords: Diabetic Neuropathy

Highlights•CSGalNAcT1-KO did not suffer from diabetic neuropathy following induced hyperglycemia•Retinal pericytes in CSGalNAcT1-KO were resistant to anti-PDGFβR•WT involved TGF-β signaling, whereas notSummaryDiabetic (DN) is a major complication of diabetes mellitus. Chondroitin sulfate (CS) one the most important extracellular matrix components and known interact with various diffusible factors; however, its role DN pathology has been examined. Therefore, we generated CSGalNAc-T1 knockout (T1KO) mice, which CS levels reduced. We demonstrated that T1KO mice much more than wild-type (WT) mice. also found interactions between vascular endothelial cells stable Among RNA-seq results, focused on transforming growth factor β signaling pathway phosphorylation Smad2/3 was less upregulated WT under hyperglycemic conditions. Taken together, reduction level attenuates progression, indicating an pathogenesis.Graphical abstract