【摘要翻译】雌激素通过转化生长因子β诱导人类前列腺基质平滑肌细胞分化

[文题]Estrogen Induction of Smooth Muscle Differentiation of Human Prostatic Stromal Cells is Mediated by Transforming Growth Factor-[beta].
雌激素通过转化生长因子β诱导人类前列腺基质平滑肌细胞分化
[来源] Journal of Urology .
[年、卷、期、页]171(5):1965-1969, May 2004
[作者]HONG, JUN HYUK; SONG, CHERYN; SHIN, YOUNJOO; KIM, HONGSIK; CHO, SEUNG PHIL; KIM, WUN-JAE; AHN, HANJONG .
[原文摘要]
ABSTRACT
Purpose: The differentiation of prostatic fibroblasts into smooth muscle cells is regarded as the key step in the development of periurethral stromal nodules. Intraprostatic stromal estrogen and transforming growth factor-[beta]1 (TGF-[beta]1) are considered to be involved in this process. We investigated whether estrogen enhances the stromal cell growth and induction of smooth muscle phenotype, and whether this process is mediated by TGF-[beta]1.

Materials and Methods: Prostate specimens obtained from patients undergoing transurethral resection of the prostate were used for primary cell culture. Growth of the prostatic stromal cells was assessed with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test and cell numbers were determined by hemocytometry. The effect of estradiol on the production of TGF-[beta]1 protein and expression of smooth muscle markers such as smooth muscle [alpha]-actin (SMA) and desmin were evaluated by Western blot and immunohistochemical staining. The mRNA levels of TGF-[beta]1 and its receptors were analyzed by reverse transcriptase-polymerase chain reaction. We also investigated whether the enhanced expression of SMA by estradiol was mediated through the TGF-[beta]1 pathway using TGF-[beta]1 blocking antibody.

Results: Estradiol promoted the proliferation of prostatic stromal cells by 10% to 20%. Estradiol and TGF-[beta]1 enhanced SMA expression. Although the levels of mRNA expression of TGF-[beta]1 or its receptors did not change after estradiol treatment, increased production of TGF-[beta]1 protein was noted. Enhanced expression of SMA by estradiol was blocked by TGF-[beta]1 blocking antibody.

Conclusions: These results suggest that estrogen stimulates the growth of prostatic stromal cells and increases smooth muscle cell markers, which may be achieved through a pathway involving TGF-[beta]1.

中文翻译:
目的：前列腺尿道部间质小瘤形成的关键是前列腺成纤维细胞向平滑肌细胞的转化，而前列腺间质内雌激素和TGFβ-1（转化生长因子β1，下面不再翻译）参与了这一过程。我们研究了雌激素是否会导致基质细胞增生，是否会诱导平滑肌细胞表型转化，以及这些过程是否由TGFβ-1介导。

材料和方法：前列腺标本采自经尿道前列腺切除的病人，将标本进行原代细胞培养。用MTT法测定前列腺间质细胞的生长，用血细胞计数器测定细胞数量。用蛋白质斑迹法（Western blot）和免疫组织化学染色法评价雌激素对转化生长因子β1的作用和平滑肌标志物如α肌动蛋白（SMA）、结蛋白水平。用RT-PCR（逆转录聚合酶链式反应）检测TGFβ-1的mRNA及其受体含量。同时我们用TGFβ-1受体阻断剂阻断TGFβ-1，以此了解雌激素使SMA表达升高是否是由TGFβ-1介导的。

结果：雌激素使前列腺间质细胞表达提高了10% ~ 20%，同时雌激素和TGFβ-1使SMA的表达增加。虽然经雌激素处理后TGFβ-1的mRNA和受体水平没有改变，但TGFβ-1的蛋白产物却有明显升高。雌激素诱导的SMA的升高能够被TGFβ-1阻滞剂阻断。

结论：结果表明雌激素能够通过TGFβ-1的介导，刺激前列腺间质细胞生长，增加平滑肌表达。

个人短评:
雌激素致良性前列腺增生的机制不清，现主要集中研究生长因子，研究结果有很大争议，国内有研究表明激素主要通过TGFβ-2介导致前列腺增生，而认为TGFβ-1不起作用，需要进一步研究证实。