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Ameliorating the Effect of Pioglitazone on LPS-Induced Inflammation of Human Oligodendrocyte Progenitor Cells

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Abstract

Oligodendrocyte progenitor cells (OPCs) are appropriate model cells for studying the progress of neurodegenerative disorders and evaluation of pharmacological efficacies of small molecules for treatment of these disorders. Here, we focused on the therapeutic role of Pioglitazone, which is a selective agonist of peroxisome proliferator-activated receptor gamma (PPARγ), a respective nuclear receptor in inflammatory responses. Human embryonic stem cell-derived OPCs were pretreated by Pioglitazone at differing concentrations. Pretreated OPCs were further examined after induction of inflammation by LPS. Interestingly, Pioglitazone reversed the inflammatory conditions and enhanced OPC viability. Data showed that Pioglitazone reduced Nitric Oxide (NO) production. Moreover, Pioglitazone enhanced cell viability through distinct mechanisms including reduction of apoptosis and regulation of cell cycle markers. This study demonstrated that NO induces apoptosis through FOXO1 and degradation of β-catenin, while the presence of Pioglitazone inhibited these effects in rescuing human OPCs from apoptosis. Also, Pioglitazone did not show a significant influence on mRNA levels of TLR2, TRL4, and TNFα. Furthermore, simultaneous treatment of Pioglitazone with CHIR, a GSKβ inhibitor, facilitated anti-apoptotic responses of OPCs. Taken together, therapy with Pioglitazone represents a novel potential drug in alleviating the loss of OPCs in neurodegenerative conditions.

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Abbreviations

15d-PGJ2:

Cyclopentenone prostaglandin 15-deoxy 12,14 prostaglandin J2

bFGF:

Basic fibroblast growth factor

EGF:

Epidermal growth factor

FITC:

Fluorescein isothiocyanate

GRM:

Glial restriction medium

GSK-3:

Glycogen synthase kinase-3

hESCs:

Human embryonic stem cells

HRP:

Horseradish peroxidase

IRF1:

Interferon regulatory factor-1

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinases

MS:

Multiple sclerosis

MTS/PMS:

[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium)/phenazine methosulfate]

NOS:

NO synthase

NSCs:

Neural stem cells

OPCs:

Oligodendrocyte progenitor cells

PBMCs:

Peripheral blood mononuclear cells

PDGF:

Platelet-derived growth factor

PHA:

Phyto-hemagglutinin

PI:

Propidium iodide

PPARγ:

Peroxisome proliferator-activated receptor γ

PVDF:

Polyvinylidene difluoride

qPCR:

Quantitative real-time PCR

RA:

Retinoic acid

STAT1:

Signal transducer and activator of transcription 1

TLR:

Toll-like receptor

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Acknowledgements

We thank our colleagues and Royan staff members for their association and helpful discussion in this project. This study was supported Royan Institute. None of the authors have any conflicts of interest to disclose and all authors support submission to this journal.

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Authors and Affiliations

  1. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

    Maryam Peymani

  2. Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

    Kamran Ghaedi

  3. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, 816513-1378, Iran

    Maryam Peymani, Kamran Ghaedi, Motahare-Sadat Hashemi, Ali Ghoochani, Abbas Kiani-Esfahani & Mohammad Hossein Nasr-Esfahani

  4. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran

    Hossein Baharvand

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  1. Maryam Peymani
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Contributions

MP contributed to the conception and design of the work, acquisition of data, analysis and interpretation of data, and drafted sections of the manuscript. M-SH contributed to the acquisition and analysis of data. AG contributed to the acquisition of data and drafted sections of the manuscript. AK-E contributed to the acquisition of data and drafted sections of the manuscript. KG contributed to the design of work, analysis and interpretation of data, and finalized the manuscript. MHN-E contributed to the design of work, analysis and interpretation of data, and finalized the manuscript. HB contributed to the design of work, analysis and interpretation of data, and finalized the manuscript.

Corresponding authors

Correspondence to Kamran Ghaedi, Mohammad Hossein Nasr-Esfahani or Hossein Baharvand.

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Peymani, M., Ghaedi, K., Hashemi, MS. et al. Ameliorating the Effect of Pioglitazone on LPS-Induced Inflammation of Human Oligodendrocyte Progenitor Cells. Cell Mol Neurobiol 38, 517–527 (2018). https://doi.org/10.1007/s10571-017-0500-6

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  • DOI: https://doi.org/10.1007/s10571-017-0500-6

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