Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Anatomy, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Iran J Med Sci. 2024 Feb 1;49(2):65-76. doi: 10.30476/ijms.2023.95425.2678. eCollection 2024 Feb.
Some studies have evaluated the manipulation of the sonic hedgehog (Shh) signaling pathway to generate more efficient insulin-producing cells (IPCs). In a systematic review, we evaluated and studies on the effect of inhibition or activation of the Shh pathway on the production, differentiation, maintenance, and endocrine activity of IPCs.
A systematic review was conducted using all available experimental studies published between January 2000 and November 2022. The review aimed at determining the effect of Shh manipulation on the differentiation of stem cells (SCs) into IPCs. Keywords and phrases using medical subject headings were extracted, and a complete search was performed in Web of Science, Embase, ProQuest, PubMed, Scopus, and Cochrane Library databases. The inclusion criteria were manipulation of Shh in SCs, SCs differentiation into IPCs, and endocrine activity of mature IPCs. Articles with incomplete data and duplications were excluded.
A total of 208 articles were initially identified, out of which 11 articles were included in the study. The effect of Shh inhibition in the definitive endoderm stage to produce functional IPCs were confirmed. Some studies showed the importance of Shh re-activation at late-stage differentiation for the generation of efficient IPCs. It is proposed that baseline concentrations of Shh in mature pancreatic β-cells affect insulin secretion and endocrine activities of the cells. However, Shh overexpression in pancreatic β-cells ultimately leads to improper endocrine function and inadequate glucose-sensing insulin secretion.
Accurate manipulation of the Shh signaling pathway can be an effective approach in the production and maintenance of functional IPCs.
一些研究评估了 sonic hedgehog（Shh）信号通路的操纵，以产生更有效的胰岛素分泌细胞（IPC）。在系统评价中，我们评估了关于抑制或激活 Shh 通路对 IPC 的产生、分化、维持和内分泌活性的影响的研究。
使用 2000 年 1 月至 2022 年 11 月期间发表的所有可用实验研究进行了系统评价。该综述旨在确定 Shh 操纵对干细胞（SCs）分化为 IPC 的影响。提取了使用医学主题词的关键词和短语，并在 Web of Science、Embase、ProQuest、PubMed、Scopus 和 Cochrane Library 数据库中进行了全面搜索。纳入标准是 Shh 在 SCs 中的操纵、SCs 分化为 IPCs 以及成熟 IPCs 的内分泌活性。排除了数据不完整和重复的文章。
最初确定了 208 篇文章，其中有 11 篇文章纳入研究。Shh 抑制在确定的内胚层阶段产生功能性 IPC 的效果得到了证实。一些研究表明，Shh 在晚期分化时重新激活对于产生高效的 IPC 非常重要。有人提出，成熟胰腺β细胞中的 Shh 基线浓度会影响胰岛素分泌和细胞的内分泌活性。然而，胰腺β细胞中 Shh 的过度表达最终会导致内分泌功能异常和葡萄糖感应胰岛素分泌不足。
准确操纵 Shh 信号通路可以成为产生和维持功能性 IPC 的有效方法。
