Pandolfi Franco, Altamura Simona, Frosali Simona, Conti Pio
Department of Internal Medicine, School of Medicine, Catholic University, Rome, Italy.
Department of Internal Medicine, School of Medicine, Catholic University, Rome, Italy.
Clin Ther. 2016 May;38(5):1017-28. doi: 10.1016/j.clinthera.2016.02.028. Epub 2016 Mar 25.
This review aimed to take stock of the current status of research on damage-associated molecular pattern (DAMP) protein. We discuss the Janus-faced role of DAMP molecules in inflammation, cancer, and tissue repair. The high-mobility group box (HMGB)-1 and adenosine triphosphate proteins are well-known DAMP molecules and have been primarily associated with inflammation. However, as we shall see, recent data have linked these molecules to tissue repair. HMGB1 is associated with cancer-related inflammation. It activates nuclear factor kB, which is involved in cancer regulation via its receptor for advanced glycation end-products (RAGE), Toll-like receptors 2 and 4. Proinflammatory activity and tissue repair may lead to pharmacologic intervention, by blocking DAMP RAGE and Toll like receptor 2 and 4 role in inflammation and by increasing their concentration in tissue repair, respectively.
We conducted a MEDLINE search for articles pertaining to the various issues related to DAMP, and we discuss the most relevant articles especially (ie, not only those published in journals with a higher impact factor).
A cluster of remarkable articles on DAMP have appeared in the literature in recent years. Regarding inflammation, several strategies have been proposed to target HMGB1, from antibodies to recombinant box A, which interacts with RAGE, competing with the full molecule. In tissue repair, it was reported that the overexpression of HMGB1 or the administration of exogenous HMGB1 significantly increased the number of vessels and promoted recovery in skin-wound, ischemic injury.
Due to the bivalent nature of DAMP, it is often difficult to explain the relative role of DAMP in inflammation versus its role in tissue repair. However, this point is crucial as DAMP-related treatments move into clinical practice.
本综述旨在评估损伤相关分子模式（DAMP）蛋白的研究现状。我们讨论了DAMP分子在炎症、癌症和组织修复中所扮演的双重角色。高迁移率族蛋白盒（HMGB）-1和三磷酸腺苷蛋白是众所周知的DAMP分子，主要与炎症相关。然而，正如我们将看到的，最近的数据已将这些分子与组织修复联系起来。HMGB1与癌症相关炎症有关。它通过其晚期糖基化终产物受体（RAGE）、Toll样受体2和4激活参与癌症调节的核因子κB。促炎活性和组织修复可能分别通过阻断DAMP、RAGE以及Toll样受体2和4在炎症中的作用，以及通过增加它们在组织修复中的浓度，从而导致药物干预。
我们在MEDLINE上搜索了与DAMP相关的各种问题的文章，并讨论了最相关的文章，特别是（即不仅是那些发表在影响因子较高的期刊上的文章）。
近年来，文献中出现了一批关于DAMP的卓越文章。关于炎症，已经提出了几种针对HMGB1的策略，从抗体到与RAGE相互作用、与完整分子竞争的重组A盒。在组织修复方面，据报道，HMGB1的过表达或外源性HMGB1的给药显著增加了血管数量，并促进了皮肤伤口、缺血性损伤的恢复。
由于DAMP的二价性质，通常很难解释DAMP在炎症中的相对作用与其在组织修复中的作用。然而，随着与DAMP相关的治疗进入临床实践，这一点至关重要。
