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Transforming growth factor beta1 mediates apoptotic activity of angiotensin II type I receptor blocker on prostate epithelium in vitro.
Prostate. 2010 Jun 01; 70(8):899-905.P

Abstract

BACKGROUND

The significant association of benign prostatic hyperplasia (BPH) and hypertension indicates a common pathophysiological factor for both diseases. Hyperactivity of the renin-angiotensin system (RAS) has been reported in BPH. Angiotensin II type I (AT1) receptor is the principal mediator of the RAS, and the antagonist, AT1 receptor blocker (ARB), can induce apoptosis in prostate epithelium cells and increase transforming growth factor beta1 (TGF-beta1) expression. We aimed to investigate the mechanism of inhibition of AT1 receptor in prostate epithelium cells and the role of TGF-beta1.

METHODS

Human prostate epithelium cell lines were treated with different concentrations of ARB (losartan) (0, 0.1, 1, 10, 100, and 1,000 microM) for 24-72 hr. Cell proliferation was analyzed by cell proliferation assay. The location of AT1 receptor was shown by immunocytohistochemistry and immunocytofluorescence study. Analysis of apoptosis was by use of terminal transferase TdT-mediated dUTP-biotin end labeling (TUNEL) and caspase 3/7 activity assay. Mitochondrial outer-membrane permeabilization was measured by JC-1 staining. The level of TGF-beta1 was determined by enzyme-linked immunosorbent assay.

RESULTS

Immunohistochemistry and immunofluorescence analysis showed AT1 receptor expressed in epithelium cells. Compared to control cultures, cultures treated with losartan for 24-72 hr showed a dose-dependent significant decrease in cell number, with apoptosis increased by 65.2%. Decreased cell number was reversed on treatment with anti-TGF-beta1 antibody. TUNEL staining showed increased apoptosis in prostate epithelium cells exposed to losartan. Caspase 3/7 activation was increased and mitochondrial membrane potential was downregulated. Expression of TGF-beta1 in cells treated with losartan was higher than that in untreated cells.

CONCLUSIONS

The apoptotic effect of blockade of AT1 receptor on human prostatic epithelium cells may be mediated through an autocrine the production of TGF-beta1. Furthermore, this finding may have implications for medication options. Inc.

Authors+Show Affiliations

Department of Urology, Peking University First Hospital, Beijing, China. zhaoyayuan@126.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20135646

Citation

Zhao, Yayuan, et al. "Transforming Growth Factor Beta1 Mediates Apoptotic Activity of Angiotensin II Type I Receptor Blocker On Prostate Epithelium in Vitro." The Prostate, vol. 70, no. 8, 2010, pp. 899-905.
Zhao Y, Peng J, Zheng L, et al. Transforming growth factor beta1 mediates apoptotic activity of angiotensin II type I receptor blocker on prostate epithelium in vitro. Prostate. 2010;70(8):899-905.
Zhao, Y., Peng, J., Zheng, L., Yu, W., & Jin, J. (2010). Transforming growth factor beta1 mediates apoptotic activity of angiotensin II type I receptor blocker on prostate epithelium in vitro. The Prostate, 70(8), 899-905. https://doi.org/10.1002/pros.21124
Zhao Y, et al. Transforming Growth Factor Beta1 Mediates Apoptotic Activity of Angiotensin II Type I Receptor Blocker On Prostate Epithelium in Vitro. Prostate. 2010 Jun 1;70(8):899-905. PubMed PMID: 20135646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transforming growth factor beta1 mediates apoptotic activity of angiotensin II type I receptor blocker on prostate epithelium in vitro. AU - Zhao,Yayuan, AU - Peng,Jing, AU - Zheng,Lanbin, AU - Yu,Wei, AU - Jin,Jie, PY - 2010/2/6/entrez PY - 2010/2/6/pubmed PY - 2010/5/14/medline SP - 899 EP - 905 JF - The Prostate JO - Prostate VL - 70 IS - 8 N2 - BACKGROUND: The significant association of benign prostatic hyperplasia (BPH) and hypertension indicates a common pathophysiological factor for both diseases. Hyperactivity of the renin-angiotensin system (RAS) has been reported in BPH. Angiotensin II type I (AT1) receptor is the principal mediator of the RAS, and the antagonist, AT1 receptor blocker (ARB), can induce apoptosis in prostate epithelium cells and increase transforming growth factor beta1 (TGF-beta1) expression. We aimed to investigate the mechanism of inhibition of AT1 receptor in prostate epithelium cells and the role of TGF-beta1. METHODS: Human prostate epithelium cell lines were treated with different concentrations of ARB (losartan) (0, 0.1, 1, 10, 100, and 1,000 microM) for 24-72 hr. Cell proliferation was analyzed by cell proliferation assay. The location of AT1 receptor was shown by immunocytohistochemistry and immunocytofluorescence study. Analysis of apoptosis was by use of terminal transferase TdT-mediated dUTP-biotin end labeling (TUNEL) and caspase 3/7 activity assay. Mitochondrial outer-membrane permeabilization was measured by JC-1 staining. The level of TGF-beta1 was determined by enzyme-linked immunosorbent assay. RESULTS: Immunohistochemistry and immunofluorescence analysis showed AT1 receptor expressed in epithelium cells. Compared to control cultures, cultures treated with losartan for 24-72 hr showed a dose-dependent significant decrease in cell number, with apoptosis increased by 65.2%. Decreased cell number was reversed on treatment with anti-TGF-beta1 antibody. TUNEL staining showed increased apoptosis in prostate epithelium cells exposed to losartan. Caspase 3/7 activation was increased and mitochondrial membrane potential was downregulated. Expression of TGF-beta1 in cells treated with losartan was higher than that in untreated cells. CONCLUSIONS: The apoptotic effect of blockade of AT1 receptor on human prostatic epithelium cells may be mediated through an autocrine the production of TGF-beta1. Furthermore, this finding may have implications for medication options. Inc. SN - 1097-0045 UR - https://www.unboundmedicine.com/medline/citation/20135646/Transforming_growth_factor_beta1_mediates_apoptotic_activity_of_angiotensin_II_type_I_receptor_blocker_on_prostate_epithelium_in_vitro_ L2 - https://doi.org/10.1002/pros.21124 DB - PRIME DP - Unbound Medicine ER -