Nephrological Center, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany; and
Pharmazentrum Frankfurt, Institute of General Pharmacology and Toxicology, Goethe-University of Frankfurt/Main, Frankfurt/Main, Germany
J Am Soc Nephrol. 2014 Jul;25(7):1387-400. doi: 10.1681/ASN.2014010117. Epub 2014 Apr 24.
Tissue injury initiates an inflammatory response through the actions of immunostimulatory molecules referred to as damage-associated molecular patterns (DAMPs). DAMPs encompass a group of heterogenous molecules, including intracellular molecules released during cell necrosis and molecules involved in extracellular matrix remodeling such as hyaluronan, biglycan, and fibronectin. Kidney-specific DAMPs include crystals and uromodulin released by renal tubular damage. DAMPs trigger innate immunity by activating Toll-like receptors, purinergic receptors, or the NLRP3 inflammasome. However, recent evidence revealed that DAMPs also trigger re-epithelialization upon kidney injury and contribute to epithelial-mesenchymal transition and, potentially, to myofibroblast differentiation and proliferation. Thus, these discoveries suggest that DAMPs drive not only immune injury but also kidney regeneration and renal scarring. Here, we review the data from these studies and discuss the increasingly complex connection between DAMPs and kidney diseases.
组织损伤通过被称为损伤相关分子模式（DAMPs）的免疫刺激分子的作用引发炎症反应。DAMPs 包含一组异质分子，包括细胞坏死过程中释放的细胞内分子以及参与细胞外基质重塑的分子，如透明质酸、biglycan 和纤维连接蛋白。肾脏特异性 DAMPs 包括晶体和由肾小管损伤释放的尿调蛋白。DAMPs 通过激活 Toll 样受体、嘌呤能受体或 NLRP3 炎性体来触发先天免疫。然而，最近的证据表明，DAMPs 在肾脏损伤时也会引发上皮再上皮化，并有助于上皮-间充质转化，可能还会促进肌成纤维细胞分化和增殖。因此，这些发现表明 DAMPs 不仅驱动免疫损伤，还驱动肾脏再生和肾脏瘢痕形成。在这里，我们回顾了这些研究的数据，并讨论了 DAMPs 与肾脏疾病之间日益复杂的联系。
