In Vitro Generated Equine Hepatic-Like Progenitor Cells as a Novel Potent Cell Pool for Equine Metabolic Syndrome (EMS) Treatment

Marycz, Krzysztof; Bourebaba, Nabila; Serwotka-Suszczak, Anna; Mularczyk, Malwina; Galuppo, Larry D.; Bourebaba, Lynda

doi:10.1007/s12015-023-10507-3

Cited by 3 publications

(4 citation statements)

References 45 publications

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“…Equine hepatic progenitor cells (HPCs) were generated using a two-step differentiation process of equine adipose-derived stromal cells (ASCs), as previously described [7,39]. Briefly, the ASCs were subjected to a 10-day differentiation process.…”

Section: Cell and Culture Conditionsmentioning

confidence: 99%

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Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs)

Qasem,

Dąbrowska,

Króliczewski

et al. 2024

Cells

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Equine metabolic syndrome (EMS) is a significant global health concern in veterinary medicine. There is increasing interest in utilizing molecular agents to modulate hepatocyte function for potential clinical applications. Recent studies have shown promising results in inhibiting protein tyrosine phosphatase (PTP1B) to maintain cell function in various models. In this study, we investigated the effects of the inhibitor Trodusquemine (MSI-1436) on equine hepatic progenitor cells (HPCs) under lipotoxic conditions. We examined proliferative activity, glucose uptake, and mitochondrial morphogenesis. Our study found that MSI-1436 promotes HPC entry into the cell cycle and protects them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the cells’ morphological architecture. Furthermore, our findings suggest that MSI-1436 enhances 2-NBDG uptake by increasing the expression of SIRT1, which is associated with liver insulin sensitivity. It also promotes mitochondrial dynamics by modulating mitochondria quantity and morphotype as well as increasing the expression of PINK1, MFN1, and MFN2. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in treating EMS and insulin dysregulation.

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Section: Cell and Culture Conditionsmentioning

confidence: 99%

“…Non-alcoholic fatty liver disease (NAFLD), a prevalent chronic liver disorder, is characterized by abnormal accumulation of triglycerides and other lipids in the liver. Liver disorders are strongly associated with insulin resistance, type 2 diabetes, obesity, and metabolic syndrome [3,7].…”

Section: Introductionmentioning

confidence: 99%

Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs)

Qasem,

Dąbrowska,

Króliczewski

et al. 2024

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…Equine hepatic progenitor cells (HPCs) have been generated using a two-step differentiation of equine adipose-derived stromal cells (ASCs) as previously described [7,43]. Briefly, the ASCs cells were subjected to a 10-days differentiation process; the cells were incubated during 2 days in DMEM-Low Glucose (LG) culture medium supplemented with 20 ng / ml of Epidermal Growth Factor (EGF) and 10 ng / ml of basic Fibroblast Growth Factor (bFGF) (conditioning step).…”

Section: Cell and Culture Conditionsmentioning

confidence: 99%

“…Nonalcoholic fatty liver disease (NAFLD), a prevalent chronic liver disorder, is characterized by the abnormal accumulation of triglycerides and other lipids in the liver. NAFLD is strongly linked to insulin resistance, type 2 diabetes, obesity, and metabolic syndrome [3,7].…”

Section: Introductionmentioning

confidence: 99%

Trodusquemine (MSI-1436) restores metabolic flexibility and mitochondrial dynamics in insulin-resistant equine hepatic progenitor cells (HPCs)

Qasem¹,

Bourebaba²,

Dąbrowska³

et al. 2023

Preprint

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Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine worldwide, and there is growing interest in utilizing molecular agents for modulation of hepatocyte function for potential clinical applications with recent studies showing promising results in the inhibition of PTP1B on adipose-derived stromal cells. In this study, we investigated the effects of MSI-1436 on equine hepatic progenitor cells (HPCs) in terms of their proliferative activity, glucose uptake, and mitochondrial morphogenesis under lipotoxic condition. Our study found that MSI-1436 promotes the entry of HPCs in the cell cycle and rescues them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the morphological architecture of the cells. Additionally, our findings suggest that MSI-1436 enhances the 2-NBDG internalization by increasing the expression of SIRT1, which is associated with liver insulin sensitivity, and promotes mitochondrial dynamics by modulating their number and morphotype through PINK1, MFN1, and MFN2 increased expression. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in the treatment of EMS and insulin dysregulation.

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From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond

Zhou,

Yao,

Lin

et al. 2024

Pharmaceutics

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Protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) regulate the level of tyrosine phosphorylation in proteins. PTKs are key enzymes that catalyze the transfer of an ATP phosphoric acid to a tyrosine residue on target protein substrates. Protein tyrosine phosphatases (PTPs) are responsible for the dephosphorylation of tyrosine residues and play a role in countering PTK overactivity. As widespread oncogenes, PTKs were once considered to be promising targets for therapy. However, tyrosine kinase inhibitors (TKIs) now face a number of challenges, including drug resistance and toxic side effects. Treatment strategies now need to be developed from a new perspective. In this review, we assess the current state of TKIs and highlight the role of PTPs in cancer and other diseases. With the advances of allosteric inhibition and the development of multiple alternative proprietary drug strategies, the reputation of PTPs as “undruggable” targets has been overturned, and they are now considered viable therapeutic targets. We also discuss the strategies and prospects of PTP-targeted therapy, as well as its future development.

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In Vitro Generated Equine Hepatic-Like Progenitor Cells as a Novel Potent Cell Pool for Equine Metabolic Syndrome (EMS) Treatment

Cited by 3 publications

References 45 publications

Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs)

Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs)

Trodusquemine (MSI-1436) restores metabolic flexibility and mitochondrial dynamics in insulin-resistant equine hepatic progenitor cells (HPCs)

From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond

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