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骨膜蛋白在皮肤发育和切口愈合过程中的时空表达:对人类纤维性瘢痕形成的启示。

Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation.

出版信息

J Cell Commun Signal. 2010 Jun;4(2):99-107. doi: 10.1007/s12079-010-0090-2. Epub 2010 May 7.

DOI:10.1007/s12079-010-0090-2
PMID:20531985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2876237/
Abstract

UNLABELLED

Differentiation of fibroblasts to myofibroblasts and collagen fibrillogenesis are two processes essential for normal cutaneous development and repair, but their misregulation also underlies skin-associated fibrosis. Periostin is a matricellular protein normally expressed in adult skin, but its role in skin organogenesis, incisional wound healing and skin pathology has yet to be investigated in any depth. Using C57/BL6 mouse skin as model, we first investigated periostin protein and mRNA spatiotemporal expression and distribution during development and after incisional wounding. Secondarily we assessed whether periostin is expressed in human skin pathologies, including keloid and hypertrophic scars, psoriasis and atopic dermatitis. During development, periostin is expressed in the dermis, basement membrane and hair follicles from embryonic through neonatal stages and in the dermis and hair follicle only in adult. In situ hybridization demonstrated that dermal fibroblasts and basal keratinocytes express periostin mRNA. After incisional wounding, periostin becomes re-expressed in the basement membrane within the dermal-epidermal junction at the wound edge re-establishing the embryonic deposition pattern present in the adult. Analysis of periostin expression in human pathologies demonstrated that it is over-expressed in keloid and hypertrophic scars, atopic dermatitis, but is largely absent from sites of inflammation and inflammatory conditions such as psoriasis. Furthermore, in vitro we demonstrated that periostin is a transforming growth factor beta 1 inducible gene in human dermal fibroblasts. We conclude that periostin is an important ECM component during development, in wound healing and is strongly associated with pathological skin remodeling.

SUMMARY

Periostin is a fibrogenic protein that mediates fibroblast differentiation and extracellular matrix synthesis. Here, we show that periostin is dynamically and temporally expressed during skin development, is induced by TGF-beta1 in vitro and is significantly upregulated during wound repair as well as cutaneous pathologies.

摘要

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成纤维细胞向肌成纤维细胞的分化和胶原原纤维的生成是正常皮肤发育和修复所必需的两个过程,但它们的失调也是皮肤相关纤维化的基础。骨粘连蛋白是一种细胞外基质蛋白,正常情况下在成人皮肤中表达,但它在皮肤器官发生、切口愈合和皮肤病理学中的作用尚未得到深入研究。我们使用 C57/BL6 小鼠皮肤作为模型,首先研究了骨粘连蛋白蛋白和 mRNA 在发育过程中和切口创伤后的时空表达和分布。其次,我们评估了骨粘连蛋白是否在人类皮肤病理学中表达,包括瘢痕疙瘩和肥厚性瘢痕、银屑病和特应性皮炎。在发育过程中,骨粘连蛋白在胚胎期到新生儿期的真皮、基底膜和毛囊中表达,并在成人期仅在真皮和毛囊中表达。原位杂交显示真皮成纤维细胞和基底角蛋白细胞表达骨粘连蛋白 mRNA。在切口创伤后,骨粘连蛋白在伤口边缘的真皮-表皮交界处的基底膜中重新表达,重新建立了成年时存在的胚胎沉积模式。对人类病理学中骨粘连蛋白表达的分析表明,它在瘢痕疙瘩和肥厚性瘢痕、特应性皮炎中过度表达,但在炎症部位和炎症性疾病如银屑病中基本不存在。此外,我们在体外证明骨粘连蛋白是人类真皮成纤维细胞中转化生长因子β 1 的诱导基因。我们得出结论,骨粘连蛋白是发育过程中、在伤口愈合中重要的细胞外基质成分,并与病理性皮肤重塑密切相关。

摘要

骨粘连蛋白是一种纤维生成蛋白,可介导成纤维细胞分化和细胞外基质合成。在这里,我们显示骨粘连蛋白在皮肤发育过程中动态和时间性地表达,在体外被 TGF-β1 诱导,并在伤口修复以及皮肤病理学中显著上调。

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Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway.骨膜蛋白通过整合素 αvβ3 和 αvβ5 及粘着斑激酶(FAK)通路介导血管平滑肌细胞迁移。
Atherosclerosis. 2010 Feb;208(2):358-65. doi: 10.1016/j.atherosclerosis.2009.07.046. Epub 2009 Jul 30.
2
Periostin localizes to cells in normal skin, but is associated with the extracellular matrix during wound repair.骨桥蛋白定位于正常皮肤中的细胞,但在伤口修复过程中与细胞外基质相关联。
J Cell Commun Signal. 2009 Jun;3(2):125-33. doi: 10.1007/s12079-009-0057-3. Epub 2009 Jun 19.
3
Periostin as a heterofunctional regulator of cardiac development and disease.骨膜蛋白作为心脏发育和疾病的多功能调节因子。
Curr Genomics. 2008 Dec;9(8):548-55. doi: 10.2174/138920208786847917.
4
Periostin promotes a fibroblastic lineage pathway in atrioventricular valve progenitor cells.骨膜蛋白促进房室瓣祖细胞中的成纤维细胞谱系途径。
Dev Dyn. 2009 May;238(5):1052-63. doi: 10.1002/dvdy.21933.
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The multifaceted role of periostin in tumorigenesis.骨膜蛋白在肿瘤发生中的多方面作用。
Cell Mol Life Sci. 2009 Jul;66(14):2219-30. doi: 10.1007/s00018-009-0013-7. Epub 2009 Mar 24.
6
Modulation of human gingival fibroblast adhesion, morphology, tyrosine phosphorylation, and ERK 1/2 localization on polished, grooved and SLA substratum topographies.在抛光、有槽和 SLA 表面形貌上,调节人牙龈成纤维细胞黏附、形态、酪氨酸磷酸化和 ERK1/2 定位。
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Periostin is essential for the integrity and function of the periodontal ligament during occlusal loading in mice.在小鼠咬合加载过程中,骨膜蛋白对于牙周韧带的完整性和功能至关重要。
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Functional role of periostin in development and wound repair: implications for connective tissue disease.骨膜蛋白在发育和创伤修复中的功能作用:对结缔组织疾病的影响。
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The epidermis: a sensory tissue.表皮:一种感觉组织。
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