GSK3 Inhibitor-BIO Regulates Proliferation of Immortalized Pancreatic Mesenchymal Stem Cells (iPMSCs)

Abstract

BackgroundThe small molecule 6-bromoindirubin-30-oxime (BIO), a glycogen synthase kinase 3 (GSK3) inhibitor, is a pharmacological agent known to maintain self-renewal in human and mouse embryonic stem cells (ESCs). However, the precise role of GSK3 in immortalized pancreatic mesenchymal stem cells (iPMSCs) growth and survival is not completely understood at present.ResultsTo determine whether this molecule is involved in controlling the proliferation of iPMSCs, we examined the effect of BIO on iPMSCs. We found that the inactivation of GSK3 by BIO can robustly stimulate iPMSCs proliferation and mass formation as shown by QRT-PCR, western blotting, 5-Bromo-2-deoxyuridine (BrdU) immunostaining assay and tunel assay. However, we did not find the related roles of BIO on β cell differentiation by immunostaining, QRT-PCR assay, glucose-stimulated insulin release and C-peptide content analysis.ConclusionsThese results suggest that BIO plays a key role in the regulation of cell mass proliferation and maintenance of the undifferentiated state of iPMSCs.

Novel Neuroprotective GSK-3β Inhibitor Restricts Tat-Mediated HIV-1 Replication

“…18BIOder is a cytoprotective small-molecule inhibitor. GSK-3␤ inhibitors have been shown to have prosurvival activity and to regulate cell proliferation in various cell types (96)(97)(98)(99). In order to exclude potential cytotoxicity of our compounds, we first assessed the effects of 18BIOder on cell viability in various cell lines, including uninfected (CEM and Jurkat) and HIV-1-infected T cells (ACH2 and J1.1) and monocytes (U937 and HIV-1-infected U1).…”

6BIO Enhances Oligonucleotide Activity in Cells: A Potential Combinatorial Anti-androgen Receptor Therapy in Prostate Cancer Cells

“…41 Blocking the activity of GSK-3b will thus elevate levels of b-catenin. 42 However, in every case, 6BIO was able to enhance oligo-directed downregulation of the targeted mRNAs. It should be noted that 6BIO did not enhance the uptake of a Cy5-labeled PS LNA gapmer ASO in LNCaP cells, as determined by flow cytometry ( Figure S3).…”

Multipotent male germline stem cells (mGSCs) from neonate porcine testis

“…After that, cells were incubated by propidium iodide (PI, Sigma, USA) solution and RNase H (Beyotime, China) for 20 min. Cell cycle analysis was determined by flow cytometry as previously reported (Cao et al 2012;Sun et al 2013). …”

“…The cultured mGSCs also express the markers of SSCs, and differentiated into spermatozoa. Porcine is a convenient domestic species for current biological investigation and application, because it has diversified products of commercial value and relatively short gestation period (Lv et al 2012). Porcine is viewed as the most promising model for human being, because it has the similar metabolism, and their physiology are close to human beings (Cao et al 2011;Lv et al 2012).…”

“…Porcine is a convenient domestic species for current biological investigation and application, because it has diversified products of commercial value and relatively short gestation period (Lv et al 2012). Porcine is viewed as the most promising model for human being, because it has the similar metabolism, and their physiology are close to human beings (Cao et al 2011;Lv et al 2012). In mammalian species other than mouse and human, where ample attempts to generate ESC lines had limited success, GSC based gene targeting is a promising technique for the production of transgenic offspring.…”