Integrins as Modulators of Transforming Growth Factor Beta Signaling in Dermal Fibroblasts During Skin Regeneration After Injury
Integrins as Modulators of Transforming Growth Factor Beta Signaling in Dermal Fibroblasts During Skin Regeneration After Injury
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DOI：
10.1089/wound.2012.0394
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发表时间：
2013-06-01
影响因子：
4.9
通讯作者：
Dagnino, Lina
中科院分区：
文献类型：
--
作者：
Boo, Stellar;Dagnino, Lina
意义：创面修复异常是肉芽组织重塑障碍的结果，可导致增生性瘢痕和纤维化。过多的疤痕会损害组织功能，降低组织对额外伤害的抵抗力。因此，开发潜在的治疗方法以减少瘢痕形成是必要的，以解决一个重要的临床问题。最近的进展：已经清楚地确定，多种细胞因子和生长因子参与皮肤伤口愈合的调节。最近，很明显，这些因素并不一定激活孤立的信号通路。相反，在某些情况下，参与这一过程的几个细胞通路存在交叉调制。在伤口愈合过程中相互调节的两个关键通路是由转化生长因子-β和通过整合素作用的细胞外基质蛋白激活的。关键问题：由于这一过程的复杂性，创伤愈合时过度瘢痕的发病机制尚不完全清楚。然而，许多途径结合在一起产生纤维化的事实提供了多个潜在的治疗靶点。其中一些已被鉴定，如粘着斑激酶和整合素连接的激酶。目前，一个主要的挑战是开发具有治疗价值的这些蛋白的药理抑制剂以促进有效的伤口修复。未来的发展方向：能够更好地了解不同途径在伤口修复过程中是如何串扰的，识别和药理调节有助于调节多条伤口愈合途径的关键因素，可能提供有效的治疗靶点，以减少或防止过度的瘢痕形成和/或纤维化的发展。
Significance: Abnormal wound repair results from disorders in granulation tissue remodeling, and can lead to hypertrophic scarring and fibrosis. Excessive scarring can compromise tissue function and decrease tissue resistance to additional injuries. The development of potential therapies to minimize scarring is, thus, necessary to address an important clinical problem.Recent Advances: It has been clearly established that multiple cytokines and growth factors participate in the regulation of cutaneous wound healing. More recently, it has become apparent that these factors do not necessarily activate isolated signaling pathways. Rather, in some cases, there is cross-modulation of several cellular pathways involved in this process. Two of the key pathways that modulate each other during wound healing are activated by transforming growth factor-beta and by extracellular matrix proteins acting through integrins.Critical Issues: The pathogenesis of excessive scarring upon wound healing is not fully understood, as a result of the complexity of this process. However, the fact that many pathways combine to produce fibrosis provides multiple potential therapeutic targets. Some of them have been identified, such as focal adhesion kinase and integrin-linked kinase. Currently, a major challenge is to develop pharmacological inhibitors of these proteins with therapeutic value to promote efficient wound repair.Future Directions: The ability to better understand how different pathways crosstalk during wound repair and to identify and pharmacologically modulate key factors that contribute to the regulation of multiple wound-healing pathways could potentially provide effective therapeutic targets to decrease or prevent excessive scar formation and/or development of fibrosis.