Yang Jincheng, Moon Hyung-Geun, Chettimada Sukrutha, Jin Yang
Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115.
J Biochem Pharmacol Res. 2014 Jun;2(2):99-109. Epub 2014 Apr 5.
As an essential organ for gas exchange, the lungs are constantly exposed to the external environment and are simulated by toxicants and pathogens. The integrity of lung epithelium and epithelial cells is crucial for fulfilling the physiological functions of the lung. The homeostasis of lung epithelial cells is maintained by a complex network by which survival and death are tightly regulated. Upon noxious stimulation, lung epithelium attempts to maintain its normal structure and function. Savage of injured cells and clearance of unsalvageable dying cells or unwanted proliferated cells constantly occur in the lung epithelium. Apoptosis, or programmed cell death, functions as a primary mechanism to discard unsalvageable cells or unwanted overgrowth. Autophagy, on the other hand, initially attempts to save and repair the injured cells. However, when the noxious stimulation is too strong and cell survival becomes unfeasible, autophagy behaves oppositely and cooperates with apoptosis, subsequently accelerates cell death. The imbalance between autophagy and apoptosis potentially leads to tumorigenesis or devastating cell death/lung injury. Therefore, the cross-talk between apoptosis and autophagy in lung epithelial cells is critical in determining the fate of epithelial cells and its balance of death/survival in response to environmental stimuli. In this review, we will focus on the current understandings of the communications between apoptosis and autophagy in lung epithelial cells. We will review multiple key regulators and their underlying mechanisms involved in the cross-talk between apoptosis and autophagy. The autophagic factors, such as the Beclin-1, ATG5, Fap-1, p62 and concentration-dependent LC3B, all closely interact with multiple apoptosis pathways. Understanding these regulations of apoptosis/autophagy cross-talk potentially provides novel targets for developing diagnostic and therapeutic strategies for many lung diseases, including lung injuries and malignancies.
作为气体交换的重要器官，肺不断暴露于外部环境中，并受到毒物和病原体的刺激。肺上皮和上皮细胞的完整性对于实现肺的生理功能至关重要。肺上皮细胞的稳态由一个复杂的网络维持，在这个网络中，细胞的存活和死亡受到严格调控。在有害刺激下，肺上皮试图维持其正常结构和功能。肺上皮中不断发生受损细胞的清除以及无法挽救的濒死细胞或不需要的增殖细胞的清除。凋亡，即程序性细胞死亡，是清除无法挽救的细胞或不需要的过度生长的主要机制。另一方面，自噬最初试图挽救和修复受损细胞。然而，当有害刺激过于强烈且细胞存活变得不可行时，自噬的作用则相反，它与凋亡协同作用，随后加速细胞死亡。自噬与凋亡之间的失衡可能导致肿瘤发生或严重的细胞死亡/肺损伤。因此，肺上皮细胞中凋亡与自噬之间的相互作用对于确定上皮细胞的命运及其在应对环境刺激时的死亡/存活平衡至关重要。在本综述中，我们将聚焦于目前对肺上皮细胞中凋亡与自噬之间相互作用的理解。我们将综述参与凋亡与自噬相互作用的多个关键调节因子及其潜在机制。自噬相关因子，如Beclin-1、ATG5、Fap-1、p62和浓度依赖性LC3B，均与多种凋亡途径密切相互作用。了解凋亡/自噬相互作用的这些调控机制可能为开发针对多种肺部疾病（包括肺损伤和恶性肿瘤）的诊断和治疗策略提供新的靶点。
