Int Neurourol J.
2020 Mar;24(1):29-40. 10.5213/inj.1938186.093.
Pioglitazone Alters the Proteomes of Normal Bladder Epithelial Cells but Shows No Tumorigenic Effects
- Affiliations
-
- 1Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- 2Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA
- 3Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- 4University of California Los Angeles, Los Angeles, CA, USA
- 5Department of Urology, Ga Cheon University College of Medicine, Incheon, Korea
- KMID: 2501347
- DOI: http://doi.org/10.5213/inj.1938186.093
Abstract
- Purpose
Pioglitazone, an antihyperglycemic drug, is widely used in diabetes mellitus patients with insulin resistance. Although pioglitazone is known to have a potential link to bladder cancer (BC), there have been contradictory results. This present study is designed to understand the regulatory mechanisms that drive the effects of pioglitazone on the bladder epithelial cells.
Methods
Labeled liquid chromatography-tandem mass spectrometry-based proteomics profiling characterized the global proteomes of normal human bladder epithelial cells treated with or without pioglitazone.
Results
This approach detected approximately 5,769 proteins in total. Of those 5,769 proteins, 124 were identified as being differentially expressed due to pioglitazone treatment. Further analysis identified 95 upregulated and 29 downregulated proteins (absolute log2 fold change >0.58 and P-value<0.05). The following functional gene enrichment analysis suggested that pioglitazone may be altering a few select biological processes, such as gene/chromatin silencing, by downregulating BMI1 (B lymphoma Mo-MLV insertion region 1 homolog), a polycomb complex protein. Further cell-based assays showed that cell adhesion molecules, epithelial-mesenchymal transition markers, and major signaling pathways were significantly downregulated by pioglitazone treatment.
Conclusions
These experimental results revealed the proteomic and biological alterations that occur in normal bladder cells in response to pioglitazone. These findings provided a landscape how bladder proteome is influenced by pioglitazone, which suggests the potential adverse effects of diabetes drugs and their links to bladder dysfunctions.
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