Progranulin (PGRN) is a multi-functional growth factor known to be involved in regulating of development, cell cycle progression, cell motility, tumorigenesis and angiogenesis. Research has revealed that PGRN is a crucial mediator of skin wound healing. Nonetheless, the role of PGRN in the fibrosis process of cutaneous wound healing has not been identified. In the present study, mice with excisional wounds were treated with si-m-PGRN or physiological saline. We observed the expression of PGRN in intact and post-injury skin by immunohistochemistry. Tissue sections of skin around the wound were performed by hematoxylin & eosin and masson's trichrome staining. After PGRN knockdown by siRNA, the expression of PGRN, collagen I (Col I), small mothers against decapentaplegic homolog 3 (Smad3), phosphorylated Smad3 (P-Smad3), transforming growth factor (TGF)-β1 and TGF-β receptor I (TβRI) were detected by real-time reverse transcription polymerase chain reaction (RT-qPCR) or Western blot. PGRN mRNA and protein expressions were increased after insult and remained above that of intact skin through day 20. Down-regulation of PGRN augmented fibrosis area, skin thickness and the expression of Col I. In addition, reduction of PGRN considerably increased the expression of TGF-β1, TβRI, Smad3 and P-Smad3. These results indicate that PGRN knockdown enhances the fibrosis degree, probably via the TGF-β/Smad signaling pathway.

中文翻译：

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PGRN的减少会增加小鼠皮肤伤口愈合过程中的纤维化。

前颗粒蛋白（PGRN）是一种多功能生长因子，已知与调节发育，细胞周期进程，细胞运动，肿瘤发生和血管生成有关。研究表明，PGRN是皮肤伤口愈合的关键介质。然而，尚未确定PGRN在皮肤伤口愈合的纤维化过程中的作用。在本研究中，切除伤口的小鼠用si-m-PGRN或生理盐水治疗。我们通过免疫组织化学观察了PGRN在完整和损伤后皮肤中的表达。伤口周围皮肤的组织切片通过苏木精和曙红和马森三色染色进行。在通过siRNA敲低PGRN后，PGRN，胶原蛋白I（Col I），对抗去能力障碍同系物3（Smad3），磷酸化Smad3（P-Smad3）的小母亲的表达，通过实时逆转录聚合酶链反应（RT-qPCR）或Western blot检测转化生长因子（TGF）-β1和TGF-β受体I（TβRI）。受伤后PGRN mRNA和蛋白表达增加，直到第20天仍保持在完整皮肤之上。PGRN的下调增加了纤维化面积，皮肤厚度和Col I的表达。此外，PGRN的降低大大增加了TGF的表达。 -β1，TβRI，Smad3和P-Smad3。这些结果表明，PGRN敲低可能通过TGF-β/ Smad信号传导途径增强了纤维化程度。受伤后PGRN mRNA和蛋白表达增加，直到第20天仍保持在完整皮肤之上。PGRN的下调增加了纤维化面积，皮肤厚度和Col I的表达。此外，PGRN的降低大大增加了TGF的表达。 -β1，TβRI，Smad3和P-Smad3。这些结果表明，PGRN敲低可能通过TGF-β/ Smad信号传导途径增强了纤维化程度。受伤后PGRN mRNA和蛋白表达增加，直到第20天仍保持在完整皮肤之上。PGRN的下调增加了纤维化面积，皮肤厚度和Col I的表达。此外，PGRN的降低大大增加了TGF的表达。 -β1，TβRI，Smad3和P-Smad3。这些结果表明，PGRN敲低可能通过TGF-β/ Smad信号传导途径增强了纤维化程度。