Medical Biochemistry Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.
Medical Biochemistry Department, Faculty of Medicine, Cairo University, POB 12613, Cairo, Egypt.
Mol Biol Rep. 2024 Jun 14;51(1):740. doi: 10.1007/s11033-024-09613-3.
Sonic Hedgehog (SHH) is a fundamental signaling pathway that controls tissue reconstruction, stem cell biology, and differentiation and has a role in gut tissue homeostasis and development. Dysregulation of SHH leads to the development of HCC.
METHODS, AND RESULTS: The present study was conducted to compare the effects of mesenchymal stem cells (MSCs) and curcumin on SHH molecular targets in an experimental model of HCC in rats. One hundred rats were divided equally into the following groups: control group, HCC group, HCC group received MSCs, HCC group received curcumin, and HCC group received MSCs and curcumin. Histopathological examinations were performed, and gene expression of SHH signaling target genes (SHH, PTCH1, SMOH, and GLI1) was assessed by real-time PCR in rat liver tissue. Results showed that SHH target genes were significantly upregulated in HCC-untreated rat groups and in MSC-treated groups, with no significant difference between them. Administration of curcumin with or without combined administration of MSCs led to a significant down-regulation of SHH target genes, with no significant differences between both groups. As regards the histopathological examination of liver tissues, both curcumin and MSCs, either through separate use or their combined use, led to a significant restoration of normal liver pathology.
In conclusion, SHH signaling is upregulated in the HCC experimental model. MSCs do not inhibit the upregulated SHH target genes in HCC. Curcumin use with or without MSCs administration led to a significant down-regulation of SHH signaling in HCC and a significant restoration of normal liver pathology.
Sonic Hedgehog（SHH）是一个基本的信号通路，控制组织重建、干细胞生物学和分化，并在肠道组织稳态和发育中发挥作用。SHH 的失调导致 HCC 的发展。
本研究旨在比较间充质干细胞（MSCs）和姜黄素对大鼠 HCC 实验模型中 SHH 分子靶标的影响。将 100 只大鼠等分为以下几组：对照组、HCC 组、HCC 组给予 MSC、HCC 组给予姜黄素、HCC 组给予 MSC 和姜黄素。进行组织病理学检查，并通过实时 PCR 评估大鼠肝组织中 SHH 信号靶基因（SHH、PTCH1、SMOH 和 GLI1）的基因表达。结果显示，未经治疗的 HCC 大鼠组和 MSC 治疗组的 SHH 靶基因显著上调，两组之间无显著差异。给予姜黄素联合或不联合 MSC 治疗导致 SHH 靶基因显著下调，两组之间无显著差异。关于肝组织的组织病理学检查，姜黄素和 MSC 无论是单独使用还是联合使用，都导致正常肝病理的显著恢复。
综上所述，SHH 信号在 HCC 实验模型中上调。MSCs 不能抑制 HCC 中上调的 SHH 靶基因。姜黄素联合或不联合 MSC 给药导致 HCC 中 SHH 信号的显著下调，并显著恢复正常肝病理。
