Morphological change and characteristics of myofibroblasts during the growth process of benign prostatic hyperplasia

Int J Urol. 2020 Aug;27(8):676-683. doi: 10.1111/iju.14265. Epub 2020 May 31.

Abstract

Objectives: To clarify the morphological change and characteristics of myofibroblast during the growth process of benign prostatic hyperplasia.

Methods: This study examined the characteristics of myofibroblasts during the growth process of the prostate in the stromal component-dominant benign prostatic hyperplasia rat model. Transforming growth factor-β1 and insulin-like growth factor-binding protein 3 expression were evaluated by western blotting (n = 6). We used double immunohistochemical staining to evaluate the number of myofibroblasts positive for α-smooth muscle actin and vimentin in benign prostatic hyperplasia tissues. Expression and histological analyses of the benign prostatic hyperplasia were also carried out in rats at 2, 3 and 8 weeks after urogenital sinus implantation (n = 6). To evaluate the fine morphological characteristics of myofibroblasts in human benign prostatic hyperplasia tissues, electron microscopy analysis was additionally carried out.

Results: There was a significant upregulation of the transforming growth factor-β1 and insulin-like growth factor-binding protein 3 expression in benign prostatic hyperplasia (P < 0.05). There was a significant increase in the number of myofibroblasts in benign prostatic hyperplasia (P < 0.05) compared with normal prostate, with these abundantly located in the stromal area. The transforming growth factor-β1 and insulin-like growth factor-binding protein 3 expression and number of myofibroblasts showed a time-dependent increase (P < 0.05), with growth factor expressions preceding the myofibroblast increase. Electron microscopy confirmed that the myofibroblast progenitor cells, which possess abundant stress fibers, were predominantly located around fibrous areas in human benign prostatic hyperplasia.

Conclusions: Differentiation into myofibroblasts induced by transforming growth factor-β1 and insulin-like growth factor-binding protein 3 actively occurs during the growth process of benign prostatic hyperplasia. Myofibroblast progenitor cells seem to be associated with prostatic fibrosis in human benign prostatic hyperplasia.

Keywords: benign prostatic hyperplasia; growth; myofibroblast; rat; transforming growth factor-β1.

MeSH terms

  • Actins
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Fibrosis
  • Humans
  • Male
  • Myofibroblasts*
  • Prostatic Hyperplasia*
  • Rats

Substances

  • Actins