ArticleStem cell research & therapy2021
MSI-1436 improves EMS adipose derived progenitor stem cells in the course of adipogenic differentiation through modulation of ER stress, apoptosis, and oxidative stress.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Inhibition of PTP1B Through NADH Dehydrogenase Activity Reduces Acute Pancreatic Acinar Cell Pyroptosis by Inhibiting the ROS/TXNIP/NLRP3 Pathway.Digestive diseases and sciences · 2026Article
- Integrated serum metabolomics reveal molecular mechanism of Xietu Hemu prescription on metabolic dysfunction-associated steatotic liver disease-related obesity.World journal of hepatology · 2025Article
- Anti-aging properties of the aminosterols of the dogfish shark.npj aging · 2024Review
- Identification of the Reference Genes for Relative qRT-PCR Assay in Two Experimental Models of Rabbit and Horse Subcutaneous ASCs.International journal of molecular sciences · 2024Article
- Article
- Endothelial Dysfunction in Obesity and Therapeutic Targets.Advances in experimental medicine and biology · 2024Review
- Novel perspectives on autophagy-oxidative stress-inflammation axis in the orchestration of adipogenesis.Frontiers in endocrinology · 2024Review
- 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 communication and signaling : CCS · 2023Article
- Can Allostery Be a Key Strategy for Targeting PTP1B in Drug Discovery? A Lesson from Trodusquemine.International journal of molecular sciences · 2023Review
- Role of Protein Tyrosine Phosphatase 1B Inhibitor in Early Brain Injury of Subarachnoid Hemorrhage in Mice.Brain sciences · 2023Article
- In Vitro Generated Equine Hepatic-Like Progenitor Cells as a Novel Potent Cell Pool for Equine Metabolic Syndrome (EMS) Treatment.Stem cell reviews and reports · 2023Article
- Article
- The PTP1B Inhibitor Trodusquemine (MSI-1436) Improves Glucose Uptake in Equine Metabolic Syndrome Affected Liver through Anti-Inflammatory and Antifibrotic Activity.International journal of inflammation · 2023Article
- The PTP1B inhibitor MSI-1436 ameliorates liver insulin sensitivity by modulating autophagy, ER stress and systemic inflammation in Equine metabolic syndrome affected horses.Frontiers in endocrinology · 2023Article
- Studying the trafficking of labeled trodusquemine and its application as nerve marker for light-sheet and expansion microscopy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Ptpn1 deletion protects oval cells against lipoapoptosis by favoring lipid droplet formation and dynamics.Cell death and differentiation · 2022Article
- Article
- PTP1B Inhibition Improves Mitochondrial Dynamics to Alleviate Calcific Aortic Valve Disease Via Regulating OPA1 Homeostasis.JACC. Basic to translational science · 2022Article
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- The Hepatic Stellate Cells (HSCs) and Adipose Derived Stem Progenitor Cells (ASCs): are they Critical Multitargeted Endogenous Metabolic Modulators in syndrome X and EMS? Letter to Editor.Stem cell reviews and reports · 2021Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProtein tyrosine phosphatase 1B (PTP1B) is one of the major negative regulators of leptin and insulin signaling, and has been strongly implicated in insulin resistance development in the course of obesity and metabolic syndrome conditions; however, its exact role in controlling adipose tissue biogenesis is still poorly understood.
objectivesThis investigation aimed to elucidate whether selective inhibition of PTP1B using MSI-1436 compound may improve and restore the defective adipogenicity of ASCs isolated from EMS-affected horses.
methodsEquine ASC EMS cells were cultured under adipogenic conditions in the presence of PTP1B inhibitor and were subsequently tested for expression of the main adipogenic-related genes using RT-qPCR, changes in free fatty acid profiles by means of GC-MS technique, and for mitochondrial dynamics improvement through the analysis of mitochondrial transmembrane potential and oxidative stress.
resultsSelective inhibition of PTP1B in equine ASC EMS cells improved substantially adipogenic differentiation by promoting cellular proliferation and normalizing expression of C/EBPalpha, PPARγ, and Adipoq markers that are critical for proper adipogenesis. Levels of secreted adiponectin and PPARγ were also shown to be increased in MSI-1436-conditioned cells, while total leptin levels markedly dropped under the same conditions. Moreover, MSI-1436 treatment enabled the regulation of metabolic-related transcripts that are crosslink to adipogenesis, namely Akt1, Akt2, and SHBG. The obtained results demonstrated also an obvious reduction in intracellular accumulated ROS and NO, as well as mitigated ER stress through the downregulation of Chop, Perk, Atf6, Ire1, and Xbp1 transcripts upon PTP1B inhibition. Furthermore, general fluctuations in FFA composition of all differentiated groups have been highlighted, where palmitic acid, palmitoleic acid, stearic acid, and linolelaidic acid that are known to be associated with the development of metabolic disorders were found to be normalized upon PTP1B inhibition during adipogenic differentiation.
conclusionThe presented data provides the evidence that the use of PTP1B inhibitor may be successful in controlling and enhancing adipogenic differentiation of impaired equine ASCs affected by metabolic syndrome, and thus offers new insights for the management of obesity through the regulation of adipose tissue dynamics.
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