Glucose-regulated protein 78 modulates cell growth, epithelial-mesenchymal transition, and oxidative stress in the hyperplastic prostate.
Xun FuJianmin LiuDaoquan LiuYongying ZhouYuhang GuoZhen WangShu YangWeixiang HePing ChenXing-Huan WangMichael E DiSantoXin-Hua ZhangPublished in: Cell death & disease (2022)
Benign prostatic hyperplasia (BPH) is a chronic condition which mainly affects elderly males. Existing scientific evidences have not completely revealed the pathogenesis of BPH. Glucose-regulated protein 78 (GRP78) is a member of the heat shock protein 70 superfamily, which serves as an important regulator in many diseases. This study aims at elucidating the role of GRP78 in the BPH process. Human prostate tissues, cultured human prostate cell lines (BPH-1 and WPMY-1) and clinical data from BPH patients were utilized. The expression and localization of GRP78 were determined with quantitative real time PCR (qRT-PCR), Western blotting and immunofluorescence staining. GRP78 knockdown and overexpression cell models were created with GRP78 siRNA and GRP78 plasmid transfection. With these models, cell viability, apoptosis rate, as well as marker levels for epithelial-mesenchymal transition (EMT) and oxidative stress (OS) were detected by CCK8 assay, flow cytometry analysis and Western blotting respectively. AKT/mTOR and MAPK/ERK pathways were also evaluated. Results showed GRP78 was localized in the epithelium and stroma of the prostate, with higher expression in BPH tissues. There was no significant difference in GRP78 expression between BPH-1 and WPMY-1 cell lines. In addition, GRP78 knockdown (KD) slowed cell growth and induced apoptosis, without effects on the cell cycle stage of both cell lines. Lack of GRP78 affected expression levels of markers for EMT and OS. Consistently, overexpression of GRP78 completely reversed all effects of knocking down GRP78. We further found that GRP78 modulated cell growth and OS via AKT/mTOR signaling, rather than the MAPK/ERK pathway. Overall, our novel data demonstrates that GRP78 plays a significant role in the development of BPH and suggests that GRP78 might be rediscovered as a new target for treatment of BPH.
Keyphrases
- benign prostatic hyperplasia
- endoplasmic reticulum stress
- lower urinary tract symptoms
- induced apoptosis
- oxidative stress
- cell surface
- signaling pathway
- epithelial mesenchymal transition
- cell proliferation
- prostate cancer
- endothelial cells
- cell cycle
- poor prognosis
- heat shock protein
- transcription factor
- flow cytometry
- real time pcr
- binding protein
- bone marrow
- deep learning
- diabetic rats
- type diabetes
- ejection fraction
- weight loss
- chronic kidney disease
- amino acid
- high throughput
- electronic health record
- long non coding rna
- single cell
- data analysis
- cell cycle arrest