Strategy of vascular protection by augmentation of endothelial glycocalyx

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08690
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Showa University
• Principal Investigator: Honda Kazuho 昭和大学, 医学部, 教授 (10256505)
• Co-Investigator(Kenkyū-buntansha): 康 徳東 昭和大学, 医学部, 講師 (00571952) ; 高木 孝士 昭和大学, 大学共同利用機関等の部局等, 准教授 (10774820)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 血管内皮 / グリコキャリックス / シアル酸 / ゲムシタビン / 糸球体内皮傷害 / 血栓性微小血管症 / 炎症性サイトカイン

Outline of Final Research Achievements

The thin layer of glycoproteins on the endothelial surface, called glycocalyx (GCX), plays an important role in maintaining the homeostasis of the vascular endothelium. We established an in-vitro endothelial injury model induced by the anticancer drug gemcitabine, and clarified changes in endothelial function by visualizing GCX and focusing on sialic acid in GCX. Lectin staining revealed that sialic acid at the end of sugar chains decreased during injury, and the expression of functional molecules such as PECAM and VEGFR2 decreased. The decrease in sialic acid was associated with decreased expression of sialyltransferase (ST6Gal1), and was accompanied by increased expression of endothelial IL-1β and IL-6 mRNA. It was suggested that changes in glycosylation in GCX may promote vascular injury through the production of inflammatory cytokines. These findings indicate that enhanced sialic acid modification of endothelial GCX may provide a clue to the development of vasoprotective therapy.

Free Research Field

腎病理学

Academic Significance and Societal Importance of the Research Achievements

抗癌剤ゲムシタビンによるin vitroの内皮傷害モデルを確立し，内皮GCXの構成要素ををレクチン(WGA、SNA、RCA-I)染色で可視化する方法を用いて，内皮傷害に関与する機能分子とその糖鎖修飾の重要性が明らかとなった。また，シアル酸修飾にはシアル酸転移酵素ST6Gal1と分解酵素NEU1の調節機構が今後の研究課題として重要であるさらに，内皮が産生するIL-1βやIL-6などの炎症性サイトカインが内皮傷害促進因子として重要であることが明らかとなった。これらの知見は，内皮傷害を背景とする動脈硬化，糖尿病，敗血症，薬剤性腎障害など多くの疾患の予防や治療に役立ち学術的ならびに社会的意義が大きい。