2. Academic Validation
  3. SGK1 inhibits oxidative injury and extracellular matrix degradation by activating the GSK-3β (Ser9)/Fyn/NRF2 pathway in pelvic organ prolapse

SGK1 inhibits oxidative injury and extracellular matrix degradation by activating the GSK-3β (Ser9)/Fyn/NRF2 pathway in pelvic organ prolapse

  • Life Sci. 2025 Aug 30:380:123939. doi: 10.1016/j.lfs.2025.123939.
Yunfang Yan 1,  Jing Peng 2,  Wei He 3,  Yan Chen 4,  Wei Ye 5,  Zongzhi Yin 6,  Yunxia Cao 7
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei 230032, Anhui, China.
  • 2 Obstetrics and Gynecology Hospital of Fudan University, No.128 Shenyang Road, Yangpu District, 200090 Shanghai, China.
  • 3 Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China.
  • 4 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China.
  • 5 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases, No 81 Meishan Road, Hefei 230032, Anhui, China.
  • 6 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases, No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address: yinzongzhi@ahmu.edu.cn.
  • 7 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address: caoyunxia5972@ahmu.edu.cn.
PMID: 40889699 DOI: 10.1016/j.lfs.2025.123939
Abstract

Aims: Sustained oxidative stress (OS) promotes the development of pelvic organ prolapse (POP); however, the pathogenesis of POP under OS conditions remains unclear. This study aimed to investigate the role of serum and glucocorticoid-induced protein kinase 1 (SGK1) in the progression of POP in OS and elucidate its potential molecular mechanisms.

Materials and methods: The protein levels of SGK1 in fibroblasts and Other cells within the uterosacral ligament tissues (ULTs) from patients with POP in OS were measured by immunofluorescence (IF). Human uterosacral ligament fibroblasts (hUSLFs) were treated with hydrogen peroxide (H2O2) to establish an in vitro model of oxidative damage. SGK1 was overexpressed and knocked down using a lentivirus to investigate oxidative damage and extracellular matrix (ECM) degradation under H2O2 stimulation. The interaction between SGK1 and GSK-3β was explored using co-immunoprecipitation assays, molecular docking models, and IF.

Key findings: SGK1 was upregulated in fibroblasts within the ULTs from patients with POP under OS conditions and in H2O2-induced hUSLFs. SGK1 overexpression in H2O2-treated hUSLFs inhibited H2O2-triggered Apoptosis, Reactive Oxygen Species generation, and Collagen loss, whereas SGK1 depletion promoted these processes. Mechanistically, SGK1 suppressed OS-induced oxidative damage, and ECM degradation in hUSLFs by binding with GSK-3β to activate the GSK-3β (Ser9)/Fyn/NRF2 pathway.

Significance: Our results revealed that SGK1 could potentially slow down the progression of POP under OS by interacting with GSK-3β to promote the GSK-3β (Ser9)/Fyn/NRF2 pathway, which provides a potential therapeutic approach for treating POP.

Keywords

Cell apoptosis; ECM degradation; GSK-3β (Ser9)/Fyn/NRF2 pathway; Oxidative stress; Pelvic organ prolapse; SGK1.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z