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Cell communication and signaling : CCS2023; 21(1); 230; doi: 10.1186/s12964-023-01254-6

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.

Abstract: 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) from apoptosis, oxidative stress, ER stress and thus improve insulin sensitivity. EqASC wells were treated with two different concentrations (50 and 100 nM) of exogenous SHBG, whose biocompatibility was tested after 24, 48 and 72 h of incubation. Several parameters including cell viability, apoptosis, cell cycle, reactive oxygen species levels, ER stress, Pi3K/MAPK activation and insulin transducers expression were analysed. 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 cells via the upregulation of MiR-7a-5p, the decrease in the expression levels of ATF-6, CHOP and eiF2A and the restoration of PDIA3 chaperone protein levels. As a consequence, SHBG application substantially improved insulin sensitivity through the modulation of Pi3K/Akt/Glut4 insulin signalling cascades. 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.
© 2023. BioMed Central Ltd., part of Springer Nature.
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Publication Date: 2023-09-11 PubMed ID: 37697311PubMed Central: PMC10496240DOI: 10.1186/s12964-023-01254-6Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the effects of sex hormone-binding globulin (SHBG) on the health and insulin sensitivity of adipose-derived stem cells in horses affected by equine metabolic syndrome (EMS). The results show that SHBG supports cell proliferation, improves cellular health, and enhances insulin sensitivity, potentially offering a new therapeutic approach for treating EMS.

Objective of the Research

  • The study aimed to determine if sex hormone-binding globulin (SHBG) could enhance the health and functionality of adipose-derived stromal stem cells (EqASC) in horses suffering from equine metabolic syndrome (EMS), a condition marked by insulin resistance and chronic inflammation. Specifically, the researchers wanted to know if SHBG could prevent cell death, reduce oxidative stress, and suppress endoplasmic reticulum (ER) stress, thereby improving insulin sensitivity.

Methodology

  • The researchers treated EqASC cells with two concentrations of SHBG (50 and 100 nM) and observed the effects after 24, 48, and 72 hours of incubation.
  • They monitored a range of indicators including cell survival, apoptosis (programmed cell death), cell cycle, levels of reactive oxygen species (which cause oxidative stress), ER stress, as well as the activation of Pi3K/MAPK pathways and insulin transducer expression.

Findings

  • SHBG treatment significantly boosted the proliferation, cycle and survival of the stem cells, along with reducing the presence of p53 and p21, proteins that promote cell death.
  • The hormone also alleviated oxidative stress associated with EMS and reduced the accumulation of reactive oxygen species within the cells. It achieved this by lowering ROS+ cell percentages and regulating the expression of endogenous antioxidant enzymes (Sod1, Cat, GPx).
  • In addition, SHBG reduced ER stress within the EqASC cells by upregulating MiR-7a-5p, decreasing the expression levels of ATF-6, CHOP and eiF2A, and restoring PDIA3 chaperone protein levels.
  • One significant outcome was that when treated with SHBG, the cells demonstrated considerably improved insulin sensitivity via the modulation of Pi3K/Akt/Glut4 insulin signalling cascades.

Conclusions

  • The results suggest that SHBG could have a positive impact on the stem cells’ metabolic activities and could potentially offer a valuable therapeutic target for creating effective treatment protocols for EMS. This stems from its capacity to support cell survival, reduce oxidative stress, mitigate ER stress, and improve insulin sensitivity.

Cite This Article

APA
Bourebaba N, Sikora M, Qasem B, Bourebaba L, Marycz K. (2023). 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. Cell Commun Signal, 21(1), 230. https://doi.org/10.1186/s12964-023-01254-6

Publication

Cell communication and signaling : CCS
ISSN: 1478-811X
NlmUniqueID: 101170464
Country: England
Language: English
Volume: 21
Issue: 1
Pages: 230
PII: 230

Researcher Affiliations

Bourebaba, Nabila
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
Sikora, Mateusz
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
Qasem, Badr
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
Bourebaba, Lynda
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
Marycz, Krzysztof
  • Department of Medicine and Epidemiology, UC Davis School of Veterinary Medicine, Davis, CA, 95516, USA. kmmarycz@ucdavis.edu.
  • Department of Veterinary Medicine and Epidemiology, Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, CA, USA. kmmarycz@ucdavis.edu.

MeSH Terms

  • Animals
  • Humans
  • Horses
  • Insulin
  • Insulin Resistance
  • Mesenchymal Stem Cells
  • Metabolic Syndrome
  • Obesity
  • Phosphatidylinositol 3-Kinases
  • Reactive Oxygen Species
  • Sex Hormone-Binding Globulin / pharmacology

Conflict of Interest Statement

Not applicable.

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