Molecular mechanisms of cystic kidney formation caused by non-centrosomal microtubule dysfunction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06645
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Waseda University
• Principal Investigator: Toya Mika 早稲田大学, 理工学術院, 准教授(任期付) (80455360)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 上皮細胞 / 微小管編成 / 腎臓 / 嚢胞腎 / 微小管マイナス端 / CAMSAP3 / 変異マウス / 遺伝子発現解析

Outline of Final Research Achievements

Renal cysts are found in approximately half of all people aged 50 and over. Most of the cysts are benign and exhibit no symptoms; however, certain genetic disorders, such as autosomal dominant polycystic kidney disease, and the associated responsible genes are known. While extensive research has been conducted on the molecular mechanisms underlying the formation of renal cysts, many aspects remain unclear. We previously found that disturbances microtubule organization of epithelial cells in renal tubule walls may lead to tubular dilation and subsequently result in cystic kidneys. This study conducted transcriptome analyses by using extracted RNA from the microtissues of mutant mice. We examined the gene expression profiles associated with the change in tissue and cell morphology in the complex structure of renal tubular microregions. The results revealed potential factors involved in the molecular mechanism of cystic kidney formation, mediated by epithelial microtubules.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

未だ多くのことが明らかになっていない腎嚢胞形成の分子メカニズムについて、新たな遺伝子発現のデータセットが得られた。今回の研究では、腎嚢胞を、尿細管の拡張、さらに、尿細管の壁を構成する上皮細胞の形態変化としてとらえた。微小領域を採取しての解析からは、組織をばらしての１細胞解析で得ることができない、組織・細胞の形態変化と遺伝子発現変動を連携させた発現遺伝子のプロファイルが得られた。進行中の解析から、細胞内の微小管編成がつかさどる嚢胞腎形成の新たな分子メカニズム、および、腎臓がその精緻な構造とそれにともなう機能を維持するしくみの理解が深まり、基礎生物学、基礎医学に貢献すると考える。