Cartilage-like composition of keloid scar extracellular matrix suggests fibroblast mis-differentiation in disease.
Cartilage-like composition of keloid scar extracellular matrix suggests fibroblast mis-differentiation in disease.
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DOI：
10.1016/j.mbplus.2019.100016
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发表时间：
2019-11
影响因子：
--
通讯作者：
Shaw TJ
中科院分区：
文献类型：
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作者：
Barallobre-Barreiro J;Woods E;Bell RE;Easton JA;Hobbs C;Eager M;Baig F;Ross AM;Mallipeddi R;Powell B;Soldin M;Mayr M;Shaw TJ
皮肤创伤后，瘢痕形成的范围很广，从可管理的正常瘢痕到病理性瘢痕疙瘩。问题仍然是这些纤维化病变是否只是代表一个数量的极端，或者，他们是否是定性不同。采用定量发现蛋白质组学方法，对正常皮肤、正常瘢痕和瘢痕疙瘩的细胞外基质（ECM）组成进行了三向比较。这种方法鉴定了40种蛋白质，与正常瘢痕相比，这些蛋白质在瘢痕疙瘩中发生了显着变化，并且引人注目的是，23种瘢痕疙瘩独特的蛋白质。瘢痕疙瘩的主要变化，当功能分组时，显示出许多参与ECM组装和纤维形成的蛋白质的变化，但也有瘢痕疙瘩相关的蛋白酶损失，以及独特的软骨样成分，这在组织学上也是明显的。瘢痕疙瘩中聚集蛋白聚糖和胶原蛋白II的存在表明组成细胞具有更大的可塑性和错误分化。这项研究的特点ECM的两种疤痕类型的深度以前低估。瘢痕疙瘩病变相对于正常瘢痕的这种彻底的分子描述是我们理解这种使人衰弱的临床问题以及如何最好地治疗它的重要一步。瘢痕疙瘩细胞外基质（ECM）在性质上不同于正常瘢痕基质。瘢痕疙瘩病变具有独特的SLRPs和FACIT胶原表达，这可能影响ECM的组织和稳定性。瘢痕疙瘩病变不适当地表达聚集蛋白聚糖和胶原蛋白II，ECM蛋白通常与软骨相关。软骨样组织表型提示疾病中成纤维细胞可塑性增强和分化不良。这些发现突出了用于治疗性破坏瘢痕ECM结构的分子靶点。
Following wound damage to the skin, the scarring spectrum is wide-ranging, from a manageable normal scar through to pathological keloids. The question remains whether these fibrotic lesions represent simply a quantitative extreme, or alternatively, whether they are qualitatively distinct. A three-way comparison of the extracellular matrix (ECM) composition of normal skin, normal scar and keloids was performed using quantitative discovery-based proteomics. This approach identified 40 proteins that were significantly altered in keloids compared to normal scars, and strikingly, 23 keloid-unique proteins. The major alterations in keloids, when functionally grouped, showed many changes in proteins involved in ECM assembly and fibrillogenesis, but also a keloid-associated loss of proteases, and a unique cartilage-like composition, which was also evident histologically. The presence of Aggrecan and Collagen II in keloids suggest greater plasticity and mis-differentiation of the constituent cells. This study characterises the ECM of both scar types to a depth previously underappreciated. This thorough molecular description of keloid lesions relative to normal scars is an essential step towards our understanding of this debilitating clinical problem, and how best to treat it. Keloid extracellular matrix (ECM) is qualitatively distinct from normal scar matrix. Keloid lesions have unique expression of SLRPs and FACIT collagens, which could affect ECM organization and stability. Keloid lesions inappropriately express Aggrecan and Collagen II, ECM proteins typically associated with cartilage. The cartilage-like tissue phenotype suggests heightened fibroblast plasticity and misdifferentiation in disease. These findings highlight molecular targets for the therapeutic disruption of the scarred ECM architecture.