Repair , Regeneration , and Fibrosis
Repair , Regeneration , and Fibrosis
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修复、再生和纤维化
DOI：
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
S. Woodward
中科院分区：
文献类型：
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作者：
G. Sephel;S. Woodward
关于伤口修复的观察结果（即，伤口愈合）可以追溯到古埃及的内科医生和古希腊的战地外科医生。肝脏的再生能力构成了希腊神话普罗米修斯的基础。凝血以防止失血被认为是伤口愈合的第一个必要事件。在美国南北战争时期，伤口出现“值得称赞的脓”被认为是必要的，它的出现并不被认为是感染的症状，而是被认为是愈合过程中的一个积极迹象。后来对伤口感染的研究发现，炎症细胞是修复过程中的主要参与者。坏血病（见第8章）早在世纪就被英国海军描述过，但直到世纪，人们才发现维生素C（抗坏血酸）对脯氨酰羟化酶的功能是必需的。脯氨酰羟化酶是一种使胶原蛋白正确折叠并稳定为三股螺旋的酶。伤口愈合的研究现在包括一个复杂的环境，包含许多细胞类型，基质蛋白，生长因子和细胞因子，调节和调节修复过程。修复过程中的几乎每个阶段都受到冗余控制，并且没有单一的限速步骤，可能的例外是炎症细胞的进入。成功的愈合维持组织功能并修复组织屏障，防止失血和感染，但通常通过胶原蛋白沉积或瘢痕形成（纤维化）来完成。我们对生长因子、细胞外基质和干细胞生物学的理解的进展正在改善愈合，并提供了使组织再生为正常结构和工程替代组织的可能性。成功的修复依赖于基质沉积的阴和基质降解的阳之间的关键平衡。当基质组成和结构不变时，再生过程是有利的。因此，不愈合的伤口可能反映了蛋白酶活性过度、基质积累减少或基质组装改变。相反，纤维化和瘢痕形成可能是由于蛋白酶活性降低或基质积累增加。虽然在修复过程中新胶原蛋白的形成是增加愈合部位强度所必需的，但慢性纤维化是涉及慢性损伤的疾病的主要组成部分。
Observations regarding the repair of wounds (i.e., wound healing) date to physicians in ancient Egypt and battle surgeons in classic Greece. The liver’s ability to regenerate forms the basis of the Greek myth involving Prometheus. The clotting of blood to prevent exsanguination was recognized as the first necessary event in wound healing. At the time of the American Civil War, the development of “laudable pus” in wounds was thought to be necessary, and its emergence was not appreciated as a symptom of infection but considered a positive sign in the healing process. Later studies of wound infection led to the discovery that inflammatory cells are primary actors in the repair process. Although scurvy (see Chapter 8) was described in the 16th century by the British navy, it was not until the 20th century that vitamin C (ascorbic acid) was found to be necessary for the function of prolyl hydroxylase, an enzyme required for proper folding and stabilization of collagen into a triple helix. The study of wound healing now encompasses a complex environment containing many cell types, matrix proteins, growth factors, and cytokines, which regulate and modulate the repair process. Nearly every stage in the repair process is redundantly controlled, and there is no single rate-limiting step, with the possible exception of the ingress of inflammatory cells. Successful healing maintains tissue function and repairs tissue barriers, preventing blood loss and infection, but is usually accomplished through collagen deposition or scarring (fibrosis). Advances in our understanding of growth factors, extracellular matrix and stem cell biology are improving healing, and offer the possibility of regenerating tissues to their normal architecture and of engineering replacement tissues. Successful repair relies upon a crucial balance between the yin of matrix deposition and the yang of matrix degradation. Regenerative processes are favored when the matrix composition and architecture are unaltered. Thus, wounds that do not heal may reflect excess proteinase activity, decreased matrix accumulation, or altered matrix assembly. Conversely, fibrosis and scarring may result from reduced proteinase activity or increased matrix accumulation. Whereas the formation of new collagen during repair is required for increased strength of the healing site, chronic fibrosis is a major component of diseases that involve chronic injury.