1. Academic Validation
  2. Inhibition of integrin receptors reduces extracellular matrix levels, ameliorating benign prostate hyperplasia

Inhibition of integrin receptors reduces extracellular matrix levels, ameliorating benign prostate hyperplasia

  • Int J Biol Macromol. 2023 Aug 31;126499. doi: 10.1016/j.ijbiomac.2023.126499.
Chengfei Yang 1 Jiang Zhao 2 Chuanchuan Lin 3 Ye Gao 2 Luo Jing 2 Fan He 2 Zhenqiang Fang 2 Zhongjun Li 4 Qian Ran 5 Zhenxing Yang 6
Affiliations

Affiliations

  • 1 Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China; Department of Thoracic Surgery, Second Affiliated Hospital, Army Medical University, Chongqing, China.
  • 2 Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China.
  • 3 Department of Blood Transfusion, Irradiation Biology Laboratory, Army Medical University, Chongqing, China.
  • 4 Department of Blood Transfusion, Irradiation Biology Laboratory, Army Medical University, Chongqing, China. Electronic address: johnneyusc@gmail.com.
  • 5 Department of Blood Transfusion, Irradiation Biology Laboratory, Army Medical University, Chongqing, China. Electronic address: louise-r-q@163.com.
  • 6 Department of Blood Transfusion, Irradiation Biology Laboratory, Army Medical University, Chongqing, China; Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China. Electronic address: yangzx88@tmmu.edu.cn.
Abstract

Although a high prevalence of benign prostate hyperplasia (BPH) has been documented, the risk factors are poorly understood. Metabolic syndrome increases the risk of BPH. Succinylation, a type of posttranslational modification, mostly targets metabolic processes. The level of succinylation was investigated in 4 BPH patients and 4 healthy controls. Additionally, 176 patients with BPH were analyzed by using pan-antisuccinyllysine antibody blotting. TMT-labeling proteomic and sc-RNAseq Cellchat analyses were employed to identify key signaling factors involved in the development of BPH. In vivo and in vitro experiments were used to confirm the role of Integrin receptors. The global succinylation level in BPH was higher than that in the healthy prostate. Positive correlations of prostate volume with IHC score sand urodynamics testing were found in large clinical cohorts. The extracellular matrix (ECM), metabolic processes and immune signaling were involved in succinylation in BPH, as indicated by using TMT-labeling proteomic analysis, and this finding was also confirmed by sc-RNAseq CellChat analysis. The proteins upregulated in SIRT5 knockout WPMY-1 cells were also enriched in the extracellular matrix and metabolic processes. More importantly, Integrin receptor inhibition in a mouse model of BPH significantly ameliorated prostate hyperplasia. High levels of succinylation modifications were found in BPH, and succinylated proteins influenced the activation of the ECM. Inhibition of ECM signaling further ameliorated prostate hyperplasia in mice.

Keywords

Benign prostate hyperplasia; Extracellular matrix; Integrin; Succinylation.

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