An Endogenous Anti-aging Factor, Sonic Hedgehog, Suppresses Endometrial Stem Cell Aging through SERPINB2

被引：31

作者：

Cho, Ara ^{[1
,2
]}

Park, Se-Ra ^{[1
,2
]}

Kim, Soo-Rim ^{[1
,2
]}

Nam, Seungyoon ^{[3
,4
]}

Lim, Soyi ^{[5
]}

Park, Chan Hum ^{[6
]}

Lee, Hwa-Yong ^{[7
]}

Hong, In-Sun ^{[1
,2
]}

机构：

[1] Gachon Univ, GAIHST, Dept Hlth Sci & Technol, Incheon 21999, South Korea

[2] Gachon Univ, Sch Med, Dept Mol Med, 7-45 Songdo Dong, Incheon 406840, South Korea

[3] Gachon Univ, Coll Med, Dept Genome Med & Sci, Incheon, South Korea

[4] Gachon Univ, Dept Life Sci, Seongnam, South Korea

[5] Gachon Univ, Gil Med Ctr, Dept Obstet & Gynecol, Incheon, South Korea

[6] Hallym Univ, Coll Med, Chuncheon Sacred Heart Hosp, Dept Otolaryngol Head & Neck Surg, Chunchon, South Korea

[7] Jungwon Univ, Dept Biomed Sci, 85 Goesan Eup, Chungcheongbuk Do 367700, South Korea

来源：

MOLECULAR THERAPY | 2019年 / 27卷 / 07期

基金：

新加坡国家研究基金会;

关键词：

ACTIVATOR INHIBITOR TYPE-2; RETINOIC ACID; PREMATURE SENESCENCE; DIFFERENTIATION; UROKINASE; MECHANISMS; PLASTICITY; INDUCTION; PROTEIN; STRESS;

D O I：

10.1016/j.ymthe.2019.04.019

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Endometrial stem cells are located in the basal layer of the endometrium, and they are responsible for the cyclic regeneration of the uterus during the menstrual cycle. Recent studies have revealed that recurrent pregnancy loss is associated with an age-related stem cell deficiency in the endometrium. Therefore, intensive study of endometrial stem cell aging may provide new insights for preventing recurrent pregnancy loss. Sonic hedgehog (SHH) signaling has been identified as a morphogen during the embryonic development processes. In addition to this canonical function, we found that the age-associated decline in regenerative potential in the endometrium may be due to decreased SHH-signaling integrity in local stem cells with aging. Importantly, the current study also showed that SHH activity clearly declines with aging both in vitro and in vivo, and exogenous SHH treatment significantly alleviates various aging-associated declines in multiple endometrial stem cell functions, suggesting that SHH may act as an endogenous anti-aging factor in human endometrial stem cells. Moreover, we found that stem cell senescence may enhance SERPINB2 expression, which in turn mediates the effect of SHH on alleviating senescence-induced endometrial stem cell dysfunctions, suggesting that SERPINB2 is a master regulator of SHH signaling during the aging process.

引用

页码：1286 / 1298

页数：13

共 48 条

[1] Relationship Between Sonic Hedgehog Protein, Brain-Derived Neurotrophic Factor and Oxidative Stress in Autism Spectrum Disorders [J].