Differentiation of human iPS cells by CCN

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06645
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Tokushima Bunri University
• Principal Investigator: Kuzuhara Takashi 徳島文理大学, 薬学部, 教授 (00260513)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: ジアジフェノライド / ヒトiPS細胞 / 神経前駆細胞 / CCN / CCN2 / 神経突起伸展 / p-44/42 MAP / リン酸化

Outline of Final Research Achievements

Comprehensive RNA sequencing showed that mRNA level expression of smooth muscle protein 22-alpha (SM22a), annexin A2 (ANXA2), CCN2, IGFBP3, and CCN1 were up-regulated, whereas those of the TP53 was down-regulated by treatment with jiadifenolide. In silico molecular network analysis showed that the up-regulated mRNA level expression of CCN, CCN1, CCN2, SM22a, ANXA2, and IGFBP3 genes were related to the regulation of SMAD, SMAD1, SMAD2, SMAD3, nuclear factor-κB (NF-κB), and STAT3 or p53. RT-qPCR showed that expression levels of CCN1, CCN2, CCN6, SM22a, and AXNA2 mRNA were significantly up-regulated in jiadifenolide-treated cells. These results showed that jiadifenolide activates CCN signaling via up-regulating the mRNA level expression of the CCN family members CCN1, CCN2, and CCN6, and CCN2 gene expression. CCN2 protein promoted neuronal dendritic outgrowth and increased neuronal cell numbers and increased phosphorylation of p44/42 MAPK protein in human neuronal precursor cells.

Free Research Field

薬学

Academic Significance and Societal Importance of the Research Achievements

骨形成因子CCNファミリータンパク質が神経分化に関与するという研究は他には全く無く世界の中でも極めて創造性が高い研究と言える。この研究を通して、神経細胞の分化と骨形成の接点が明らかになる可能性がある。