Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Endocrinology. 2021 Mar 1;162(3). doi: 10.1210/endocr/bqaa232.
Multicellular organisms have evolved sophisticated mechanisms to recover and maintain original tissue functions following injury. Injury responses require a robust transcriptomic response associated with cellular reprogramming involving complex gene expression programs critical for effective tissue repair following injury. Steroid receptor coactivators (SRCs) are master transcriptional regulators of cell-cell signaling that is integral for embryogenesis, reproduction, normal physiological function, and tissue repair following injury. Effective therapeutic approaches for facilitating improved tissue regeneration and repair will likely involve temporal and combinatorial manipulation of cell-intrinsic and cell-extrinsic factors. Pleiotropic actions of SRCs that are critical for wound healing range from immune regulation and angiogenesis to maintenance of metabolic regulation in diverse organ systems. Recent evidence derived from studies of model organisms during different developmental stages indicates the importance of the interplay of immune cells and stromal cells to wound healing. With SRCs being the master regulators of cell-cell signaling integral to physiologic changes necessary for wound repair, it is becoming clear that therapeutic targeting of SRCs provides a unique opportunity for drug development in wound healing. This review will provide an overview of wound healing-related functions of SRCs with a special focus on cellular and molecular interactions important for limiting tissue damage after injury. Finally, we review recent findings showing stimulation of SRCs following cardiac injury with the SRC small molecule stimulator MCB-613 can promote cardiac protection and inhibit pathologic remodeling after myocardial infarction.
多细胞生物已经进化出了复杂的机制，在受伤后能够恢复和维持组织的原有功能。损伤反应需要一个强大的转录组反应，与细胞重编程有关，涉及到复杂的基因表达程序，这些程序对于受伤后的有效组织修复至关重要。甾体受体共激活剂（SRCs）是细胞间信号的主要转录调节因子，对于胚胎发生、生殖、正常生理功能和受伤后的组织修复都是必不可少的。有效的治疗方法可能涉及对细胞内在和外在因素进行时间和组合的操纵，以促进改善组织再生和修复。SRCs 的多效性作用对于伤口愈合至关重要，从免疫调节和血管生成到维持不同器官系统的代谢调节。来自不同发育阶段的模式生物研究的最新证据表明，免疫细胞和基质细胞的相互作用对于伤口愈合非常重要。由于 SRCs 是细胞间信号的主要调节因子，对于伤口修复所需的生理变化至关重要，因此，靶向 SRCs 的治疗方法为伤口愈合的药物开发提供了一个独特的机会。本综述将概述 SRCs 与伤口愈合相关的功能，特别关注对于限制受伤后组织损伤的细胞和分子相互作用。最后，我们回顾了最近的发现，表明在心肌梗死后，用 SRC 小分子刺激剂 MCB-613 刺激 SRCs 可以促进心脏保护和抑制病理性重塑。
