Pleiotrophin modulates cell proliferation, prostate smooth muscle contraction and fibrosis in hyperplastic prostate

Benign prostatic hyperplasia (BPH) is a common disease afflicting elderly males all over the world. The existing scientific research still has not completely clarified its etiology. Pleiotrophin (PTN) is a developmental regulatory protein involved in various biological processes. This study aimed to elucidate the expression, biological function, and underlying mechanism of PTN in the onset and progression of BPH.

Human prostate tissues, cell lines, rat models and PTN-knockout mice models were utilized. PTN knockdown, PTN overexpression, and estradiol cell models were established. The qRT-PCR, Western Blot, flow cytometry, CCK-8 assay, collagen gel contraction assay, co-immunoprecipitation, immunofluorescence, H&E, Masson's trichrome, immunohistochemical staining, TUNEL assay and tissue micro-array analysis were performed during in vivo and in vitro experiments.

Our current data validated that PTN is localized in stroma and epithelium of the prostate, with stronger expression in BPH tissues. Functionally, silenced PTN promoted cell apoptosis while it inhibited cell proliferation, cell contraction and fibrosis. Consistently, overexpression of PTN suppressed cell apoptosis, and facilitated cell proliferation, cell contraction, as well as fibrosis. More importantly, AKT phosphorylation and RhoA/ROCK1/2 axis were confirmed to be involved in the regulation of prostate biological processes by PTN. Moreover, estradiol treatment could enhance PTN expression and modulate downstream biological process. Also, PTN expression was correlated with prostate volume (PV), fPSA and the ratio of fPSA/tPSA. Finally, recombinant PTN induced prostatic hyperplasia in rats, PTN knockout suppressed BPH in mice, and estradiol treatment upregulated PTN expression. These results further confirm the crucial role of PTN in BPH onset and progression.

Our current study demonstrates that PTN is of significance in the onset and development of BPH and may be a new target for the treatment of BPH.