Sonic Hedgehog, a Novel Endogenous Damage Signal, Activates Multiple Beneficial Functions of Human Endometrial Stem Cells.,Molecular Therapy

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Sonic Hedgehog, a Novel Endogenous Damage Signal, Activates Multiple Beneficial Functions of Human Endometrial Stem Cells.
Molecular Therapy ( IF 12.1 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.ymthe.2019.11.024
Se-Ra Park ₁ , Soo-Rim Kim ₁ , Chan Hum Park ₂ , Soyi Lim ₃ , Seung Yeon Ha ₄ , In-Sun Hong ₁ , Hwa-Yong Lee ₅

Affiliation

Local endometrial stem cells play an important role in regulating endometrial thickness, which is an essential factor for successful embryo implantation and pregnancy outcomes. Importantly, defects in endometrial stem cell function can be responsible for thin endometrium and subsequent recurrent pregnancy losses. Therefore, many researchers have directed their efforts toward finding a novel stimulatory factor that can enhance the regenerative capacity of endometrial stem cells. Sonic hedgehog (SHH) is a morphogen that plays a key role in regulating pattern formation throughout embryonic limb development. In addition to this canonical function, we identified for the first time that SHH is actively secreted as a stem cell-activating factor in response to tissue injury and subsequently stimulates tissue regeneration by promoting various beneficial functions of endometrial stem cells. Our results also showed that SHH exerts stimulatory effects on endometrial stem cells via the FAK/ERK1/2 and/or phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. More importantly, we also observed that endometrial stem cells stimulated with SHH showed markedly enhanced differentiation and migratory capacities and subsequent in vivo therapeutic effects in an endometrial ablation animal model.

中文翻译：

声波刺猬（Sonic Hedgehog）是一种新型的内源性损伤信号，可激活人子宫内膜干细胞的多种有益功能。

局部子宫内膜干细胞在调节子宫内膜厚度中起着重要作用，而子宫内膜干细胞是成功植入胚胎和妊娠结果的重要因素。重要的是，子宫内膜干细胞功能的缺陷可能导致子宫内膜变薄和随后的反复妊娠丢失。因此，许多研究者已将他们的努力转向寻找可以增强子宫内膜干细胞再生能力的新型刺激因子。声波刺猬（SHH）是一种形态发生子，在整个胚胎肢体发育过程中，在调节模式形成中起关键作用。除了此规范功能外，我们首次发现SHH可以作为组织损伤的干细胞激活因子而被积极分泌，并随后通过促进子宫内膜干细胞的各种有益功能来刺激组织再生。我们的研究结果还表明，SHH通过FAK / ERK1 / 2和/或磷脂酰肌醇3-激酶（PI3K）/ Akt信号通路对子宫内膜干细胞产生刺激作用。更重要的是，我们还观察到用SHH刺激的子宫内膜干细胞在子宫内膜消融动物模型中显示出明显增强的分化和迁移能力以及随后的体内治疗作用。

更新日期：2019-12-06

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