Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Int J Mol Sci. 2018 Jul 10;19(7):2013. doi: 10.3390/ijms19072013.
In contrast to the general belief that regeneration is a rare event, mainly occurring in simple organisms, the ability of regeneration is widely distributed in the animal kingdom. Yet, the efficiency and extent of regeneration varies greatly. Humans can recover from blood loss as well as damage to tissues like bone and liver. Yet damage to the heart and brain cannot be reversed, resulting in scaring. Thus, there is a great interest in understanding the molecular mechanisms of naturally occurring regeneration and to apply this knowledge to repair human organs. During regeneration, injury-activated immune cells induce wound healing, extracellular matrix remodeling, migration, dedifferentiation and/or proliferation with subsequent differentiation of somatic or stem cells. An anti-inflammatory response stops the regenerative process, which ends with tissue remodeling to achieve the original functional state. Notably, many of these processes are associated with enhanced glycolysis. Therefore, peroxisome proliferator-activated receptor (PPAR) β/δ—which is known to be involved for example in lipid catabolism, glucose homeostasis, inflammation, survival, proliferation, differentiation, as well as mammalian regeneration of the skin, bone and liver—appears to be a promising target to promote mammalian regeneration. This review summarizes our current knowledge of PPARβ/δ in processes associated with wound healing and regeneration.
与普遍认为再生是一种罕见事件、主要发生在简单生物体中的观点相反，再生能力在动物界中广泛分布。然而，再生的效率和程度差异很大。人类可以从失血以及骨骼和肝脏等组织的损伤中恢复过来。然而，心脏和大脑的损伤是无法逆转的，导致疤痕形成。因此，人们非常有兴趣了解自然发生的再生的分子机制，并将这些知识应用于修复人类器官。在再生过程中，损伤激活的免疫细胞诱导伤口愈合、细胞外基质重塑、迁移、去分化和/或增殖，随后体细胞或干细胞分化。抗炎反应会停止再生过程，最终通过组织重塑达到原始的功能状态。值得注意的是，其中许多过程与增强的糖酵解有关。因此，过氧化物酶体增殖物激活受体 (PPAR)β/δ——已知其参与例如脂质分解代谢、葡萄糖稳态、炎症、存活、增殖、分化以及皮肤、骨骼和肝脏的哺乳动物再生——似乎是促进哺乳动物再生的一个有前途的靶点。这篇综述总结了我们目前对与伤口愈合和再生相关过程中的 PPARβ/δ 的了解。
