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

作者：Peymani Maryam; Ghaedi Kamran^*; Hashemi Motahare Sadat; Ghoochani Ali; Kiani Esfahani Abbas; Nasr Esfahani Mohammad Hossein^*; Baharvand Hossein^*

来源：Cellular and Molecular Neurobiology, 2018, 38(2): 517-527.

DOI：10.1007/s10571-017-0500-6

• beta-Catenin
• CHIR
• Inflammation
• Oligodendrocyte progenitor cells
• Pioglitazone

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 (PPAR gamma), 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 beta-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 TNF alpha. Furthermore, simultaneous treatment of Pioglitazone with CHIR, a GSK beta 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.

• 出版日期2018-3