Roles of endotoxin derived from gut microbiota in vascular calcification associated with chronic kidney disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09731
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka City University
• Principal Investigator: SHIOI ATSUSHI 大阪市立大学, 大学院看護学研究科, 教授 (90260801)
• Co-Investigator(Kenkyū-buntansha): 森岡 与明 大阪市立大学, 大学院医学研究科, 講師 (30382154) ; 庄司 哲雄 大阪市立大学, 大学院医学研究科, 准教授 (40271192)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 動脈石灰化 / 慢性腎臓病 / 血管平滑筋細胞

Outline of Final Research Achievements

We investigated the roles of lipopolysaccharide (LPS) derived from intestinal bacteria in the development of vascular calcification in chronic kidney disease (CKD). Aortic medial calcified lesions were analyzed in LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ mice with adenine-induce CKD. Alizarin red-stained calcified lesions were more prevalent in C3H/HeJ than C3H/HeN mice. Biochemical data revealed that
renal impairment, hypocalcemia, and hyperphosphatemia are less severe in C3H/HeJ than C3H/HeN mice. On the other hand, we examined the effects of LPS on in vitro calcification of human aortic smooth muscle cells (HASMCs). In vitro calcification and alkaline phosphatase (ALP) activities in HASMC cultures were dose-dependently increased by LPS treatment. ALP mRNA levels were also up-regulated by LPS. Therefore, LPS may play an important role in the development of vascular calcification. However, its role in CKD-induced vascular calcification remains to be clarified.

Free Research Field

代謝内分泌

Academic Significance and Societal Importance of the Research Achievements

本研究によりエンドトキシン(LPS)の血管石灰化における重要性が明らかにされた。エンドトキシンは慢性腎臓病だけでなく、様々な代謝性疾患(肥満、糖尿病、脂質代謝異常症など)における動脈硬化症の危険因子として注目されている。血管石灰化はこれらの動脈硬化性疾患の発症・進展にも深く関わっていることから、血管石灰化におけるLPSの臨床的意義を明らかにすることは今後の重要な課題である。