Sex Hormone-Binding Globulin (SHBG) Mitigates ER Stress and Improves Viability and Insulin Sensitivity in Adipose-Derived Mesenchymal Stem Cells (ASC) of Equine Metabolic Syndrome (EMS)-Affected Horses

Authors

Nabila Bourebaba
Mateusz Sikora
Badr Qasem
Lynda Bourebaba
Krzysztof Marycz

Publication Date

9-11-2023

Journal

Cell Communication and Signaling

Abstract

BACKGROUND: Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adipose-derived stromal stem cells (EqASC

METHODS: EqASC

RESULTS: Obtained data demonstrated that exogenous SHBG treatment significantly promoted ASCs cells proliferation, cell cycle and survival with reduced expression of p53 and p21 pro-apoptotic mediators. Furthermore, SHBG alleviated the oxidative stress caused by EMS and reduced the overaccumulation of intracellular ROS, by reducing ROS + cell percentage and regulating gene expression of endogenous antioxidant enzymes (Sod 1, Cat, GPx), SHBG treatment exhibited antioxidant activity by modulating total nitric oxide (NO) levels in EMS cells as well. SHBG treatment dampened the activation of ER stress sensors and effectors in EqASC

CONCLUSION: Our results suggest that the SHBG is endowed with crucial beneficial effects on ASCs metabolic activities and could serve as a valuable therapeutic target for the development of efficient EMS treatment protocols. Video Abstract.

Keywords

EMS, ASC, SHBG, ER Stress, Apoptosis, PDIA3, Insulin resistance

Comments

Supplementary Materials

Video Abstract video file.(56M, mp4)

PMID: 37697311