Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, via Vanvitelli, 32 - 20129, Milan, Italy.
Center for Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, via Vanvitelli, 32 - 20129, Milan, Italy.
Exp Eye Res. 2022 Jun;219:109060. doi: 10.1016/j.exer.2022.109060. Epub 2022 Apr 4.
Corneal disorders are frequent, involving most diabetic patients; among its manifestations, they include delayed wound healing. Since maintenance of mitochondrial homeostasis is fundamental for the cell, stimulation of mitochondrial biogenesis represents a unique therapeutic tool for preventing and treating disorders with a deficit in energy metabolism. We have recently demonstrated that a branched-chain amino acid (BCAA)-enriched mixture (BCAAem) supported mitochondrial biogenesis in cardiac and skeletal muscle, reduced liver damage caused by alcohol, and prevented the doxorubicin-dependent mitochondrial damage in cardiomyocytes. The present study aimed to investigate a new amino acid mixture, named six amino acids (6AA), to promote corneal epithelial wound healing by regulating mitochondrial biogenesis. A murine epithelium cell line (TKE2) exposed to this mixture showed increased mitochondrial biogenesis markers, fibronectin 1 (Fn1) and integrin beta 1 (ITGB1) involved in extracellular matrix synthesis and cell migration. Most importantly, the 6AA mixture completely restored the wound in scratch assays, confirming the potential of this new formula in eye disorders like keratopathy. Moreover, our results demonstrate for the first time that peroxisome proliferator-receptor γ coactivator 1 α (PGC-1α) is expressed in TKE2 cells, which controls mitochondrial function and corneal repair process. These results could be relevant for the treatment mainly focused on corneal re-epithelialisation.
角膜疾病较为常见，多数糖尿病患者都会受到影响；其表现之一为伤口愈合延迟。由于维持线粒体的内稳态对细胞至关重要，因此刺激线粒体生物发生代表了一种独特的治疗工具，可以预防和治疗能量代谢不足的疾病。我们最近证明，富含支链氨基酸（BCAA）的混合物（BCAAem）可支持心脏和骨骼肌中的线粒体生物发生，减轻酒精引起的肝损伤，并预防蒽环类药物引起的心肌细胞中线粒体损伤。本研究旨在研究一种新的氨基酸混合物，称为 6 种氨基酸（6AA），通过调节线粒体生物发生来促进角膜上皮伤口愈合。暴露于该混合物的小鼠上皮细胞系（TKE2）显示出更多的线粒体生物发生标志物，如细胞外基质合成和细胞迁移所涉及的纤连蛋白 1（Fn1）和整合素β 1（ITGB1）。最重要的是，6AA 混合物完全恢复了划痕实验中的伤口，证实了这种新配方在角膜病变等眼部疾病中的潜力。此外，我们的研究结果首次证明，过氧化物酶体增殖物激活受体 γ 共激活因子 1α（PGC-1α）在 TKE2 细胞中表达，其可控制线粒体功能和角膜修复过程。这些结果可能与主要集中在角膜再上皮化的治疗方法有关。
