硅橡胶硬度通过自噬调控成纤维细胞增殖及α-SMA、CollagenⅠ的表达

王海淋; 高扬; 石小花; 杜依晨; 张一鸣; 樊东力

doi:10.16016/j.1000-5404.201811069

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硅橡胶硬度通过自噬调控成纤维细胞增殖及α-SMA、CollagenⅠ的表达

基础医学 | 更新时间：2026-01-09

- 硅橡胶硬度通过自噬调控成纤维细胞增殖及α-SMA、CollagenⅠ的表达
- Silicone rubber hardness regulates fibroblasts proliferation and expression of α-SMA and CollagenⅠ by autophagy
- 第三军医大学学报 2019年41卷第9期页码：829-835
- 作者机构：
  
  1.400037 重庆，陆军军医大学(第三军医大学)第二附属医院整形美容外科
  2.401120 重庆，重庆医科大学附属第三医院皮肤整形美容中心
- 作者简介：
  
  [樊东力，E-mail:dlfan4612@163.comFAN Dongli, E-mail:dlfan4612@163.com
- 基金信息：
  
  国家自然科学基金重点项目(81372075);第三军医大学科技成果转化基金(2012XZH05)
- DOI：10.16016/j.1000-5404.201811069
  中图分类号： R318.08;R322.991;R329.28
- 收稿：2018-11-10，
  
  修回：2019-01-31，
  
  纸质出版：2019-05-15
- 稿件说明：
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王海淋, 高扬, 石小花, 等. 硅橡胶硬度通过自噬调控成纤维细胞增殖及α-SMA、CollagenⅠ的表达[J]. 第三军医大学学报, 2019,41(9):829-835.

Hailin WANG, Yang GAO, Xiaohua SHI, et al. Silicone rubber hardness regulates fibroblasts proliferation and expression of α-SMA and CollagenⅠ by autophagy[J]. Journal of Third Military Medical University, 2019, 41(9): 829-835.
王海淋, 高扬, 石小花, 等. 硅橡胶硬度通过自噬调控成纤维细胞增殖及α-SMA、CollagenⅠ的表达[J]. 第三军医大学学报, 2019,41(9):829-835. DOI： 10.16016/j.1000-5404.201811069.

Hailin WANG, Yang GAO, Xiaohua SHI, et al. Silicone rubber hardness regulates fibroblasts proliferation and expression of α-SMA and CollagenⅠ by autophagy[J]. Journal of Third Military Medical University, 2019, 41(9): 829-835. DOI： 10.16016/j.1000-5404.201811069.

摘要

目的

探讨不同硬度硅橡胶对人真皮成纤维细胞增殖及其表达α-SMA和CollagenⅠ的影响，并研究自噬在其中所起的作用。

方法

将A、B组分液体硅胶按不同比例混合固化制成一系列不同硬度的硅橡胶片，测定其邵氏硬度、断裂伸长率、水接触角、表面形貌等机械性能。利用CCK-8检测成纤维细胞在不同硬度硅橡胶表面的增殖情况，而后选取细胞增殖存在显著差异的两种硬度硅橡胶进一步实验，采用Western blot和ELISA法分别检测正常条件下、施加自噬抑制剂3-MA和诱导剂西罗莫司后成纤维细胞自噬标志蛋白和α-SMA、Collagen Ⅰ的表达情况。

结果

成纤维细胞增殖能力随硅橡胶硬度的增加而增加，差异有统计学意义(

0.05)。高硬度硅橡胶上的成纤维细胞具有更高的自噬活性，且α-SMA、Collagen I的表达量比低硬度硅橡胶更低，差异有统计学意义(

0.01)。

结论

硅橡胶硬度可通过自噬调控成纤维细胞的增殖，高硬度硅橡胶上调成纤维细胞自噬活性从而促进成纤维细胞增殖并抑制其表达α-SMA和CollagenⅠ。

Abstract

Objective

To investigate the effect of different hardness of silicone rubber (SRs) on the proliferation and expression of α- SMA and Collagen Ⅰ in human dermal fibroblasts (HFBs)

and study the role of autophagy in the process.

Methods

In this study

we prepared a series of SRs with different hardness by changing the ratio of liquid silica gel component A to B. The mechanical properties of SRs such as A-shore hardness

breaking elongation

water contact angle and surface morphology were measured. CCK-8 assay was used to study the proliferation of HFBs cultivated on the surface of these SRs. Then

2 kinds of SRs with significant differences in hardness and cell proliferation were subjected

and Western blotting and ELISA were employed to detect the expression of autophagy markers

α-SMA and CollagenⅠin the HFBs after the treatment with autophagy inhibitor 3-MA and inducer rapamycin respectively.

Results

The proliferation of HFBs was obviously increased with the increase of SRs hardness (

0.05). Furthermore

the HFBs cultured on harder SRs surface had higher autophagy activity

and lower expression levels of α-SMA and Collagen Ⅰ when compared with the cells on softer SRs surface (

0.01).

Conclusion

The SRs hardness may affect the proliferation of HFBs by regulating autophagy. High hardness SRs promotes the proliferation of HFBs and inhibits the expression of α-SMA and CollagenⅠby enhancing autophagy activity.

关键词

Keywords

references

BUI J M, PERRY T, REN C D, et al . Erratum to: histological characterization of human breast implant capsules[J ] . Aesthetic Plast Surg, 2015, 39(3): 316-317. DOI:10.1007/s00266-015-0473-0.

TOMASEK J J, GABBIANI G, HINZ B, et al . Myofibroblasts and mechano-regulation of connective tissue remodelling[J ] . Nat Rev Mol Cell Biol, 2002, 3(5): 349-363. DOI:10.1038/nrm809.

FUSCO S, PANZETTA V, EMBRIONE V, et al . Crosstalk between focal adhesions and material mechanical properties governs cell mechanics andfunctions[J ] . Acta Biomater, 2015, 23: 63-71. DOI:10.1016/j.actbio.2015.05.008.

GILMORE A P.Anoikis[J]. Cell Death Differ, 2005, 12(Suppl 2): 1473-1477. DOI:10.1038/sj.cdd.4401723.

HAUSMANN M, LEUCHT K, PLONER C, et al . BCL-2 modifying factor (BMF) is a central regulator of anoikis in human intestinal epithelial cells[J ] . J Biol Chem, 2011, 286(30): 26533-26540. DOI:10.1074/jbc.M111.265322.

FUNG C, LOCK R, GAO S Z, et al . Induction of autophagy during extracellular matrix detachment promotes cell survival[J ] . Mol Biol Cell, 2008, 19(3): 797-806. DOI:10.1091/mbc.e07-10-1092.

LI H Y, PENG X, WANG Y T, et al . Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2/M arrest and renal fibrosis[J ] . Autophagy, 2016, 12(9): 1472-1486. DOI:10.1080/15548627.2016.1190071.

SANEYASU T, AKHTAR R, SAKAI T K. Molecular cuesguiding matrix stiffness in liver fibrosis[J]. Biomed Res Int, 2016, 2016: 2646212. DOI:10.1155/2016/2646212.

HERUM K M, LUNDE I G, MCCULLOCH A D, et al . The soft and hard-heartedness of cardiac fibroblasts:mechano-transduction signaling pathways in fibrosis of the heart[J ] . J Clin Med, 2017, 6(5): E53. DOI:10.3390/jcm6050053.

HANDORF A M, ZHOU Y X, HALANSKI M A, et al . Tissue stiffness dictates development, homeostasis, and disease progression[J ] . Organogenesis, 2015, 11(1): 1-15. DOI:10.1080/15476278.2015.1019687.

MIHAYLOVA MM, SHAW R J. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism[J]. Nat Cell Biol, 2011, 13(9): 1016-1023. DOI:10.1038/ncb2329.

VLAHAKIS A, DEBNATH J. The interconnections between autophagy and integrin-mediated cell adhesion[J]. J Mol Biol, 2017, 429(4): 515-530. DOI:10.1016/j.jmb.2016.11.027.

NEW J, ARNOLD L, ANANTH M, et al . Secretory autophagy in cancer-associated fibroblasts promotes head and neck cancer progression and offers a novel therapeutic target[J ] . Cancer Res, 2017, 77(23): 6679-6691. DOI:10. 1158/0008-5472.CAN-17-1077.

MOWERS E, SHARIFI N, MACLEOD F. Autophagy in cancer metastasis[J]. Oncogene, 2017, 36(12): 1619-1630. DOI:10.1038/onc.2016.333.

ONG C T, KHOO Y T, MUKHOPADHYAY A, et al . MTOR as a po tential therapeutic target for treatment of keloids and excessive scars[J ] .Exp Dermatol, 2007, 16(5): 394-404. DOI:10.1111/j.1600-0625.2007.00550.x.

KIM S I, NA H J, DING Y, et al . Autophagy promotes intracellular degradation of type I collagen induced by transforming growth factor (TGF)-β1[J ] . J Biol Chem, 2012, 287(15): 11677-11688. DOI:10.1074/jbc.M111.308460.

DING Y, KIM S L, LEE S Y, et al . Autophagy regulates TGF-β expression and suppresses kidney fibrosis induced by unilateral ureteral obstruction[J ] . J Am Soc Nephrol, 2014, 25(12): 2835-2846. DOI:10.1681/ASN.2013101068.

LIU B Y, KILPATRICK J I, LUKASZ B, et al. Increased substrate stiffness elicits a myofibroblastic phenotype in human lamina cribrosa cells[J]. Invest Ophthalmol Vis Sci, 2018, 59(2): 803-814. DOI:10.1167/iovs.17-22400.

SCHLUNCK G, HAN H, WECKER T, et al. Substrate rigidity modulates cell matrix interactions and protein expression in human trabecular meshwork cells[J]. Invest Ophthalmol Vis Sci, 2008, 49(1): 262-269. DOI:10.1167/iovs.07-0956.

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