Platelet-derived growth factor C is upregulated in human uterine fibroids and regulates uterine smooth muscle cell growth.
Platelet-derived growth factor C is upregulated in human uterine fibroids and regulates uterine smooth muscle cell growth.
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血小板源性生长因子 C 在人子宫肌瘤中表达上调，并调节子宫平滑肌细胞的生长。
DOI：
10.1095/biolreprod.109.076869
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发表时间：
2009
影响因子：
3.6
通讯作者：
Wang,JeanYJ
中科院分区：
文献类型：
--
作者：
Suo,Guangli;Jiang,Yong;Cowan,Bryan;Wang,JeanYJ
子宫平滑肌瘤（即，子宫肌瘤）是由子宫平滑肌细胞（SMC）的异常生长引起的良性肿瘤。我们发现，血小板源性生长因子C（PDGFC）的表达在约80%的子宫肌瘤中高于邻近的子宫肌层组织。与子宫肌层平滑肌细胞（mSMC）相比，在子宫肌瘤平滑肌细胞（fSMC）中也观察到PDGF表达增加。重组生物活性PDGFCC同二聚体刺激fSMC和mSMC在离体培养物中的生长，并抑制fSMC在免疫受损小鼠皮下实施的基质胶塞中的存活。通过慢病毒介导的RNA干扰敲低PDGF受体-α（PDGFRA）减少了离体培养物和基质胶植入物中fSMC和mSMC的生长。此外，PDGFR酪氨酸激酶的两种小分子抑制剂（即，伊马替尼和达沙替尼）对离体培养物中的fSMC和mSMC生长产生负面影响，尽管在体内不能达到的浓度下。这些结果表明，PDGFCC/PDGFRA信号模块在fSMC和mSMC的生长中起着重要作用，并且PDGFC表达的上调可能有助于fSMC在子宫肌瘤发展中的克隆扩增。
Leiomyomata uteri (i.e., uterine fibroids) are benign tumors arising from the abnormal growth of uterine smooth muscle cells (SMCs). We show here that the expression of platelet-derived growth factor C (PDGFC) is higher in approximately 80% of uterine fibroids than in adjacent myometrial tissues examined. Increased expression ofPDGFCis also observed in fibroid-derived SMCs (fSMCs) relative to myometrial-derived SMCs (mSMCs). Recombinant bioactive PDGFCC homodimer stimulates the growth of fSMCs and mSMCs in ex vivo cultures and prolongs the survival of fSMCs in Matrigel plugs implemented subcutaneously in immunocompromised mice. The knockdown of PDGF receptor-alpha (PDGFRA) through lentiviral-mediated RNA interference reduces the growth of fSMCs and mSMCs in ex vivo cultures and in Matrigel implants. Furthermore, two small molecule inhibitors of the PDGFR tyrosine kinase (i.e., imatinib and dasatinib) exerted negative effects on fSMC and mSMC growth in ex vivo cultures, albeit at concentrations that cannot be achieved in vivo. These results suggest that the PDGFCC/PDGFRA signaling module plays an important role in fSMC and mSMC growth, and that the upregulation of PDGFC expression may contribute to the clonal expansion of fSMCs in the development of uterine fibroids.