Li Lishuang, Ma Yuman, He Gaiying, Ma Shuhua, Wang Yi, Sun Yanan
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.
Biomed Pharmacother. 2023 May;161:114510. doi: 10.1016/j.biopha.2023.114510. Epub 2023 Mar 15.
Granulation tissue has supporting and filling functions in wound healing. The collagen produced by fibroblast acts as a cell scaffold in the granulation tissue to facilitate the formation of new blood vessels and epithelial coverage. Previously, we extracted protein components from the pilose antler that was involved in the biological process of collagen fibril organization. They were also found to contain abundant extracellular matrix(ECM) components. Therefore, in this experiment, we used a rat model of full-thickness skin excision and fibroblasts to perform an experiment for determination of the effects of pilose antler protein extract (PAE) on collagen content and fiber synthesis during wound healing. Additionally, we further analyzed its pharmacological effects on wound healing and the possible regulatory mechanisms. We found that PAE accelerated synthesis of type I and III collagen, promoted the formation of type III collagen fibers, and reduced collagen degradation by recruiting fibroblasts. Furthermore, the extract upregulated the expression of TGF β R1 and Smad2, and initiated the entry of Smad2/Smad3 into the nucleus. After adding SB431542 to inhibit TGF-β type I receptor activity, PAE's ability to promote Smad2/Smad3 nuclear localization was weakened. These data indicate that local PAE therapy can promote the proliferation of fibroblasts, dynamically regulate the expression of TGF-β, and increase the amount of collagen and the synthesis of type III collagen fibers by promoting smad2 activity in the proliferation period, thus accelerating the regenerative healing of wounds.
肉芽组织在伤口愈合中具有支持和填充功能。成纤维细胞产生的胶原蛋白在肉芽组织中充当细胞支架,以促进新血管的形成和上皮覆盖。此前,我们从鹿茸中提取了参与胶原纤维组织生物过程的蛋白质成分。它们还被发现含有丰富的细胞外基质(ECM)成分。因此,在本实验中,我们使用全层皮肤切除大鼠模型和成纤维细胞进行实验,以确定鹿茸蛋白提取物(PAE)对伤口愈合过程中胶原蛋白含量和纤维合成的影响。此外,我们进一步分析了其对伤口愈合的药理作用及可能的调节机制。我们发现,PAE通过募集成纤维细胞加速了I型和III型胶原蛋白的合成,促进了III型胶原纤维的形成,并减少了胶原蛋白的降解。此外,该提取物上调了TGFβR1和Smad2的表达,并促使Smad2/Smad3进入细胞核。在添加SB431542抑制TGF-βI型受体活性后,PAE促进Smad2/Smad3核定位的能力减弱。这些数据表明,局部PAE治疗可促进成纤维细胞增殖,动态调节TGF-β的表达,并通过在增殖期促进Smad2活性增加胶原蛋白量和III型胶原纤维的合成,从而加速伤口的再生愈合。