多效生长因子PTN调控前列腺平滑肌动静力因素的机制研究

良性前列腺增生症（BPH）是一种老年常见病，但发病机制不清，现有药物不能完全阻止其进展；雌激素及多效生长因子（PTN）均是研究热点，涉及多种疾病的发生发展。我们前期实验显示PTN在BPH前列腺组织中高表达，并且PTN可以调控前列腺平滑肌增殖水平以及收缩舒张能力；与此同时，雌二醇（E2）与PTN的表达成正相关，是通过ERα正向调控PTN的表达。因此提出如下假说：E2通过ERα调控PTN的转录激活，进而介导MLCK/MLCP信号通路增强平滑肌细胞收缩张力，并通过磷酸化PI3K及MAPK信号通路关键分子调节平滑肌细胞增殖凋亡水平。本研究以原代培养的人前列腺平滑肌细胞、Ptn基因敲除C57BL/6J小鼠以及人增生前列腺组织为研究对象，旨在阐明PTN对前列腺平滑肌动静力因素的调控作用以及E2对PTN的调控机制。

Benign prostatic hyperplasia (BPH) is a very common illness. But the pathogenesis remains unclear and existing drugs cannot completely prevent its progress. Moreover, it is less studied. Estrogen and pleiotrophin (PTN) are research hotspots in recent decades, involving in the occurrence and development of a variety of diseases. Our preliminary experiments show that the PTN are highly expressed in BPH prostate tissue and PTN could regulate the proliferation and contraction of prostatic smooth muscle. Meanwhile, there is a positive relationship between PTN and serum estradiol (E2), and PTN is found being positively regulated by E2 via ERα. Therefore, we hypothesised that E2 might regulate the expression of PTN through ERα. Meanwhile, PTN might have an impact on contraction of prostatic smooth muscle via MLCK/MLCP signaling pathways, and PTN might regulate cell proliferation through PI3K and MAPK signaling pathways. In current study, primary cultured human prostatic smooth muscle cells, Ptn knockout C57BL/6J mice and hyperplasia prostate tissue were used to explore the dynamic and static function of PTN on prostate smooth muscle and to explore the molecular mechanisms of E2 regulating PTN.