1 Department of Oral Physiology, BK21 PLUS Project, and Institute of Translational Dental Sciences, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.
2 Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration, and School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
J Dent Res. 2016 Nov;95(12):1415-1424. doi: 10.1177/0022034516659642. Epub 2016 Jul 28.
This study aimed to investigate the role of PIN1 on the hepatic differentiation of human dental pulp stem cells (hDPSCs) and its signaling pathway, as well as the potential therapeutic effects of hDPSC transplantation and PIN1 inhibition on CCl (carbon tetrachloride)-induced liver fibrosis in mice. The in vitro results showed that hepatic differentiation was suppressed by infection with adenovirus-PIN1 and promoted by PIN1 inhibitor juglone via the downregulation of Wnt3a and β-catenin. Compared with treatment with either hDPSC transplantation or juglone alone, the combination of hDPSCs and juglone into CCl-injured mice significantly suppressed liver fibrosis and restored serum levels of alanine transaminase, aspartate transaminase, and ammonia. Collectively, the present study shows for the first time that PIN1 inhibition promotes hepatic differentiation of hDPSCs through the Wnt/β-catenin pathway. Furthermore, juglone in combination with hDPSC transplantation effectively treats liver fibrosis, suggesting that hDPSC transplantation with PIN1 inhibition may be a novel therapeutic candidate for the treatment of liver injury.
本研究旨在探讨 PIN1 在人牙髓干细胞（hDPSCs）肝向分化中的作用及其信号通路，以及 hDPSC 移植和 PIN1 抑制剂对 CCl（四氯化碳）诱导的小鼠肝纤维化的潜在治疗作用。体外实验结果表明，腺病毒-PIN1 感染抑制肝向分化，而 PIN1 抑制剂 Juglone 通过下调 Wnt3a 和 β-连环蛋白促进其分化。与单独 hDPSC 移植或 Juglone 治疗相比，hDPSCs 和 Juglone 联合应用于 CCl 损伤的小鼠可显著抑制肝纤维化，并恢复血清丙氨酸转氨酶、天冬氨酸转氨酶和氨水平。综上所述，本研究首次表明，PIN1 抑制通过 Wnt/β-连环蛋白通路促进 hDPSCs 的肝向分化。此外，Juglone 联合 hDPSC 移植可有效治疗肝纤维化，提示抑制 PIN1 的 hDPSC 移植可能是治疗肝损伤的一种新的治疗候选物。
