Leptin promotes epithelial-mesenchymal transition in benign prostatic hyperplasia through downregulation of BAMBI.

Abstract

Benign prostatic hyperplasia (BPH) is a common disease in older men, and there is evidence that obesity is a causal factor. It is currently unclear whether the hormone leptin, which is positively correlated to obesity, is involved in BPH. The aim of this study was to determine the effect of leptin on testosterone-induced BPH in mice and to explore possible underlying mechanisms. Testosterone (3 mg/kg) was injected into wild-type and leptin-deficient ob/ob male mice for 14 consecutive days, and prostate tissues were subjected to various analyses. Additionally, BPH epithelial-1 (BPH-1) cells were treated with leptin to further investigate the underlying mechanisms. Leptin deficiency attenuated testosterone-induced morphological and pathological changes of BPH in mice. Furthermore, leptin deficiency alleviated the process of epithelial-mesenchymal transition (EMT) and suppressed the downregulation of bone morphogenic protein and activin membrane-bound inhibitor (BAMBI) in testosterone-treated mice. The in vitro data revealed that leptin significantly increased the expression of the EMT-associated marker vimentin but decreased the expression of E-cadherin, and that upregulation of BAMBI mitigated the intensity of leptin-induced EMT responses. Our results suggest that leptin can promote EMT in BPH through downregulating BAMBI. Suppressing leptin might be a potential therapeutic approach in preventing BPH development and progression.

• Authors: Bo Zhang, Xiang Chen, Chaoqun Xie, Zhi Chen, Yuhang Liu, Feng Ru, Yao He
• Journal: Experimental cell research (Exp Cell Res) Vol. 387 Issue 1 Pg. 111754 (02 01 2020) ISSN: 1090-2422 [Electronic] United States
• PMID: 31805276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Bambi protein, mouse
• Cadherins
• Leptin
• Membrane Proteins
• Vimentin
• Testosterone

Topics

• Animals
• Cadherins (metabolism)
• Cell Line
• Disease Models, Animal
• Down-Regulation (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Humans
• Leptin (pharmacology)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Prostate (drug effects, metabolism)
• Prostatic Hyperplasia (metabolism)
• Signal Transduction (drug effects)
• Testosterone (metabolism)
• Up-Regulation (drug effects)
• Vimentin (metabolism)