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Volume 37 Issue 10
Oct.  2021
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2021  >  37(10): 937-945
Zhu DZ,Yao B,Cui XL,et al.Effects and mechanism of age on the stiffness and the fibrotic phenotype of fibroblasts of human hypertrophic scar[J].Chin J Burns,2021,37(10):937-945.DOI: 10.3760/cma.j.cn501120-20200810-00374.
Citation: Zhu DZ,Yao B,Cui XL,et al.Effects and mechanism of age on the stiffness and the fibrotic phenotype of fibroblasts of human hypertrophic scar[J].Chin J Burns,2021,37(10):937-945.DOI: 10.3760/cma.j.cn501120-20200810-00374.
shu

Effects and mechanism of age on the stiffness and the fibrotic phenotype of fibroblasts of human hypertrophic scar

doi: 10.3760/cma.j.cn501120-20200810-00374
  • 1.

    Research Center for Wound Repair and Regeneration, Medical Innovation Research Department, the PLA General Hospital, Beijing 100048, China

  • 2.

    Key Laboratory of Tissue Repair and Regeneration of PLA, Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, the Fourth Medical Center, the PLA General Hospital, Beijing 100048, China

Funds:

General Program of National Natural Science Foundation of China 32000969, 82002056

Military Medicine Innovation Research program of Chinese PLA General Program CX19026

Wang Zhengguo Foundation for Traumatic Medicine Growth Factor Rejuvenation Plan SZYZ-TR-03

More Information
  • Corresponding author: Huang Sha, Email: stellarahuang@sina.com
  • Received Date: 2020-08-10
    Abstract
  •   Objective  To explore the effects and potential molecular mechanism of age on the stiffness and the fibrotic phenotype of fibroblasts (Fbs) of human hypertrophic scar.  Methods  The experimental research method was used. From January to June 2020, the surgically removed hypertrophic scar tissue of 10 scar patients (4 males and 6 females) and residual full-thickness normal skin tissue of 10 cases (5 males and 5 females, aged 7-41 years) were collected after operation in Department of Burns and Plastic Surgery of the Fourth Medical Center of the PLA General Hospital. The hypertrophic scar tissue of 6 patients aged (10.7±1.6) years was included into the young group and the hypertrophic scar tissue of 4 patients aged (40.0±2.2) years was included into the elderly group according to the age of patients. For the normal skin tissue and scar tissue in the two groups, hematoxylin eosin (HE) staining was performed to observe the tissue morphology, Masson staining was performed to observe the morphology and arrangement of collagen and quantify the content of collagen, and scanning electron microscope was used to observe the microscopic difference of dermal collagen fibers after the samples were freeze-dried and metal coated. The stiffness of scar tissue in the two groups was measured by atomic force microscope under the liquid phase. The scar tissue in the two groups was collected and the Fbs were isolated and cultured. The morphological differences of the Fbs were observed under the inverted phase contrast microscope, and the protein expression of paxillin was detected with cellular immunofluorescence to reflect the morphology of the Fbs. Cellular immunofluorescence was used to detect the expressions of pro-fibrosis protein α-smooth actin (α-SMA), transforming growth factor-β1 (TGF-β1), and type Ⅰ collagen, mechanotransduction-related protein Yes-associated protein (YAP), and the proliferation-related protein Ki67. Real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to detect the mRNA expressions of pro-fibrosis genes of TGF-β1, α-SMA, and type Ⅰ collagen, fibrosis inhibiting gene of TGF-β3, and mechanotransduction-related genes of Rho-associated protein 1 (ROCK1) and YAP. Data were statistically analyzed with one-way analysis of variance and least significant difference t test.  Results  HE staining showed that the epidermal layer of normal skin was uneven, and blood vessels and sweat glands could be seen in the dermal layer; the epidermal layer of the scar tissue in the two groups was relatively flat, and blood vessels and sweat glands were rare. Masson staining and scanning electron microscopy showed that the collagen fibers in normal skin arranged loosely and disorderly, while the collagen fibers in scar tissue of the two groups arranged densely and orderly, and the collagen fibers in scar tissue of the young group were denser than those of the elderly group. The collagen content in scar tissue of the young group and the elderly group was significantly higher than that of the normal skin tissue (t=8.02, 3.15, P<0.05 or P<0.01), and the collagen content in scar tissue of the elderly group was significantly lower than that of the young group (t=4.84, P<0.05). The dermal stiffness of scar tissue in the elderly group was (50.3±1.1) kPa, significantly higher than (35.2±0.8) kPa in the young group (t=11.43, P<0.05). There were no obvious differences in the morphology of scar Fbs in the two groups observed under inverted phase contrast microscope and by cellular immunofluorescence. The expressions of type Ⅰ collagen and TGF-β1 in scar Fbs cytoplasm of the elderly group were significantly higher than those in the young group, while the expressions of α-SMA in scar Fbs cytoplasm were close in the two groups. The expressions of YAP in cytoplasm and nucleus of scar Fbs in the elderly group were significantly higher than those in the young group, while the expressions of Ki67 in scar Fbs nucleus of the two groups were close. The mRNA expressions of TGF-β1 and type Ⅰ collagen in scar Fbs of the elderly group were significantly higher than those in the young group (t=2.87, 4.85, P<0.05 or P<0.01), the mRNA expression of TGF-β3 in scar Fbs of the elderly group was significantly lower than that in the young group (t=3.36, P<0.05), and the mRNA expressions of α-SMA in scar Fbs of the two groups were close (t=1.14, P>0.05). The mRNA expressions of ROCK1 and YAP in scar Fbs of the elderly group were significantly higher than those in the young group (t=2.98, 7.60, P<0.05 or P<0.01).  Conclusions  The elderly are prone to scar healing after skin injury. The molecular mechanism may be attributed to the production of extracellular matrix components with higher stiffness, which increases tissue stiffness and thereby activates the expressions of ROCK and YAP/transcriptional co-activator with PDZ-binding motif genes, promoting pro-fibrosis gene and protein expression.

     

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    Created with Highcharts 5.0.7Chart context menuAccess Area Distribution其他: 5.3 %其他: 5.3 %其他: 1.3 %其他: 1.3 %Australia: 0.2 %Australia: 0.2 %China: 1.4 %China: 1.4 %United States: 0.3 %United States: 0.3 %三明: 0.2 %三明: 0.2 %上海: 2.0 %上海: 2.0 %东莞: 0.5 %东莞: 0.5 %临汾: 0.2 %临汾: 0.2 %伊犁: 0.2 %伊犁: 0.2 %佛山: 0.2 %佛山: 0.2 %加利福尼亚州: 0.2 %加利福尼亚州: 0.2 %北京: 2.8 %北京: 2.8 %北方邦: 0.5 %北方邦: 0.5 %南京: 0.5 %南京: 0.5 %南昌: 1.1 %南昌: 1.1 %呼和浩特: 0.2 %呼和浩特: 0.2 %哈尔滨: 0.3 %哈尔滨: 0.3 %哥伦布: 0.5 %哥伦布: 0.5 %商洛: 0.2 %商洛: 0.2 %嘉兴: 0.2 %嘉兴: 0.2 %大同: 0.2 %大同: 0.2 %天津: 0.8 %天津: 0.8 %太原: 0.2 %太原: 0.2 %安庆: 0.6 %安庆: 0.6 %宣城: 0.5 %宣城: 0.5 %密蘇里城: 0.3 %密蘇里城: 0.3 %广州: 1.3 %广州: 1.3 %张家口: 3.0 %张家口: 3.0 %悉尼: 0.2 %悉尼: 0.2 %成都: 0.5 %成都: 0.5 %拉贾斯坦邦: 0.5 %拉贾斯坦邦: 0.5 %昆明: 0.5 %昆明: 0.5 %普赖恩维尔: 0.2 %普赖恩维尔: 0.2 %杭州: 0.6 %杭州: 0.6 %武汉: 0.6 %武汉: 0.6 %沃思堡: 0.3 %沃思堡: 0.3 %沈阳: 0.3 %沈阳: 0.3 %洛阳: 0.2 %洛阳: 0.2 %济南: 1.3 %济南: 1.3 %海得拉巴: 0.5 %海得拉巴: 0.5 %深圳: 1.1 %深圳: 1.1 %温州: 0.2 %温州: 0.2 %漯河: 0.9 %漯河: 0.9 %石家庄: 0.3 %石家庄: 0.3 %绵阳: 1.3 %绵阳: 1.3 %芒廷维尤: 50.2 %芒廷维尤: 50.2 %芜湖: 0.6 %芜湖: 0.6 %芝加哥: 0.3 %芝加哥: 0.3 %苏州: 0.8 %苏州: 0.8 %荆州: 0.5 %荆州: 0.5 %葵涌: 0.3 %葵涌: 0.3 %西宁: 2.7 %西宁: 2.7 %西安: 1.4 %西安: 1.4 %运城: 0.2 %运城: 0.2 %遵义: 0.2 %遵义: 0.2 %邯郸: 0.2 %邯郸: 0.2 %重庆: 6.4 %重庆: 6.4 %银川: 0.5 %银川: 0.5 %长沙: 0.9 %长沙: 0.9 %阜阳: 0.2 %阜阳: 0.2 %青岛: 0.5 %青岛: 0.5 %韶关: 0.2 %韶关: 0.2 %香港: 0.2 %香港: 0.2 %其他其他AustraliaChinaUnited States三明上海东莞临汾伊犁佛山加利福尼亚州北京北方邦南京南昌呼和浩特哈尔滨哥伦布商洛嘉兴大同天津太原安庆宣城密蘇里城广州张家口悉尼成都拉贾斯坦邦昆明普赖恩维尔杭州武汉沃思堡沈阳洛阳济南海得拉巴深圳温州漯河石家庄绵阳芒廷维尤芜湖芝加哥苏州荆州葵涌西宁西安运城遵义邯郸重庆银川长沙阜阳青岛韶关香港

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      沈阳化工大学材料科学与工程学院 沈阳 110142

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