自噬对烧伤创面愈合的影响

细胞自噬是细胞在应激状态下应用溶酶体对自身损伤细胞器等物质进行分解,将产生的大分子物质予以回收利用,从而保留细胞活性的降解过程。自噬在细胞的发育和分化进程中起着至关重要的作用。烧伤创面经历炎症期、细胞增殖期和组织重塑期3个时期完成组织愈合。细胞自噬在烧伤创面愈合过程中,具有促进病原体清除,参与新生血管增殖、肉芽组织形成,改善上皮的角质化以及瘢痕重塑的作用。调控自噬,可影响烧伤创面愈合。本文综述细胞自噬在烧伤创面愈合中的研究进展。     

流体剪切力调节血管内皮细胞自噬的研究进展

细胞自噬作为细胞的一种防御和应激调控机制,参与维持细胞的代谢平衡。在血管内皮细胞中,自噬是影响内皮细胞功能的一个重要因素。流体剪切力也是影响血管内皮细胞形态和功能的重要因素之一。而血管内皮细胞生理功能的维持在整个心血管系统的正常运转中起着重要的作用。我们主要对血管内皮细胞的功能,细胞自噬和流体剪切力对血管内皮细胞功能的调节作用,以及流体剪切力对血管内皮细胞自噬的调节作用等方面进行综述。     

自噬与肿瘤血管生成的研究进展

自噬（autophagy）是一种特殊的细胞过程,可通过将自身受损的细胞器和大分子物质转运至溶酶体并降解,参与调控细胞存活、生长、分化和内环境稳态的维持,在生命过程的各个方面均起着非常重要的作用。研究结果发现,自噬在肿瘤发生、发展及转移过程中起着重要作用,其与血管内皮生长因子协同作用促进肿瘤的血管生成和细胞修复,且可能在...     

氧化应激与自噬在糖尿病血管并发症中的相互作用

血管损伤是糖尿病患者的常见并发症,血管内皮细胞的功能障碍是导致糖尿病血管损伤的主要危险因素。自噬是正常细胞在生长周期中必不可少的维持体内稳态的生理过程,其主要功能是细胞器回收和蛋白质的降解,异常自噬的发生将导致细胞线粒体的损伤并进而促进细胞死亡。内皮细胞线粒体是活性氧(ROS)产生的主要部位,糖尿病引起的高糖血症使细胞氧化应激水平升高,ROS产生增加,导致血管内皮细胞功能障碍。ROS可诱导细胞过度自噬,使内皮细胞发生凋亡与坏死,从而引起血管损伤。本文将对ROS及其诱导的过度自噬在促进糖尿病血管并发症中的病理生理作用和研究作一综述。     

细胞自噬与心血管疾病

细胞自噬是一种利用溶酶体对自身细胞器进行分解、将产生的大分子物质予以回收利用的高度保守的细胞降解过程。饥饿、缺血、氧化应激等均可诱导其发生。自噬在细胞的发育和分化过程中起着至关重要的作用,和许多心血管疾病的发生、发展密切相关。正常的细胞自噬对心肌细胞有保护作用,自噬不足或自噬过度则可促发疾病或加重病变。本文综述细胞自噬在心血管疾病中的研究进展。     

细胞自噬与动脉粥样硬化关系的研究进展

自噬是一种降解病原体和相关细胞器尤其是损伤的线粒体的分子机制,自噬也可清除其他的细胞成分,例如炎症和细胞因子,这为抗炎症提供了重要的途径.相关研究发现,自噬的产生或降解能够影响动脉粥样硬化斑块的发展过程.因此,在疾病出现时,自噬的调节对于疾病治疗的靶点具有重要的意义.然而,在正常情况和炎症反应时,自噬的调节方式是多方面的.这些错综复杂的改变是通过炎症和环境刺激所产生的,这对于了解和揭示自噬调节的炎症和提供相应的治疗方案是必不可少的.因而人了解自噬的分子机制,以及血管内皮细胞、血管平滑肌细胞、巨噬细胞自噬在动脉粥样硬化中起到的作用对于疾病的发展和靶向治疗具有重要意义.     

细胞自噬参与病毒免疫关键环节

细胞自噬作为哺乳动物细胞内的一个具有高度保守性的活动过程,是维持细胞稳态的基本代谢活动,也是细胞面临不利条件时确保细胞自身生存的重要手段。面对病毒的入侵,根据病毒种类、细胞种类以及细胞应激反应的不同,自噬既可以发挥抗病毒作用,也可能会被病毒利用。因此,了解自噬在病毒免疫过程中发挥的作用对于发展新型抗病毒治疗和预防有着重要的意义。在此基础上,本文旨在介绍自噬参与的病毒免疫环节来探讨自噬的抗病毒免疫作用。     

肾癌中细胞自噬的作用及自噬调节剂在肾癌治疗中的研究进展

细胞自噬是细胞体内的一种“自我吞噬”的分解代谢过程,通过将细胞内衰老的细胞器、受损蛋白和其他细胞成分包裹于自噬溶酶体中,从而实现能量供应和物质的循环利用。研究表明,细胞自噬与肾癌的发生、发展和转归密切相关,其不仅参与肾癌的发生,而且在肾癌发展的不同阶段分别起促进或抑制的双重作用。有针对性地靶向调节不同阶段肾癌的自噬水平可能是治疗肾癌的新策略。该文对细胞自噬的发生过程及其在肾癌发展进程中的作用进行综述,并探讨自噬调节剂(自噬抑制剂/诱导剂)在肾癌治疗中的潜在作用。     

自噬在破骨细胞分化过程中的调控作用

破骨细胞在骨吸收过程中发挥着重要作用,其形成和功能失调可参与骨质疏松、类风湿性关节炎等多种骨相关疾病的发生。破骨细胞的形成和分化是一个复杂的生物学过程,其调控机制尚未完全明了。本研究旨在探讨自噬在破骨细胞分化过程中的作用。在RANKL刺激下,小鼠巨噬细胞RAW264.7可被诱导分化为破骨细胞。本研究采用TRAP染色法检测RAW264.7细胞向破骨细胞分化进程中抗酒石酸酸性磷酸酶活性变化,并通过Western blotting技术检测分析自噬相关蛋白LC3表达变化;并应用自噬抑制剂3-甲基腺嘌呤(3-Methyladenine,3-MA)明确自噬在破骨细胞分化中的作用。30ng/ml的RANKL刺激RAW264.7细胞至第5d时可观察到分化成熟的破骨细胞。在此过程中,RANKL刺激至第3d时细胞自噬作用显著增强,此后(如第5d时)自噬作用则逐渐减弱。在分化过程中如果以3-MA抑制细胞的自噬,RAW264.7细胞向破骨细胞的分化则可被显著抑制。可见,自噬在RANKL介导的破骨细胞分化成熟的过程中发挥重要的调控作用,抑制自噬则阻碍破骨细胞的分化成熟。     

细胞自噬在病毒感染与免疫过程中的作用

自噬是细胞维持内环境稳态的一种保护机制,不仅调节细胞代谢,在应激条件下,自噬通过降解并回收利用细胞成分促进细胞存活。在病毒感染过程中,自噬作为监督机制将病毒抗原传递给富含免疫感应器的内体/溶酶体,激活固有免疫反应,自噬还可加工提呈病毒抗原激活适应性免疫反应,此外,自噬体本身就可降解病毒。然而,病毒为了逃避自噬,也进化出许多阻止自噬的方式。由于自噬的抗病毒作用,人们期望利用自噬对微生物感染进行治疗。本文对自噬在抗病毒免疫中的作用及其潜在应用价值的研究进展进行综述。     

Autophagy in SDF-1α-mediated DPSC migration and pulp regeneration

Critical morphological requirements for pulp regeneration are tissues replete with vascularisation, neuron formation, and dentin deposition. Autophagy was recently shown to be related to angiogenesis, neural differentiation, and osteogenesis. The present study aimed to investigate the involvement of autophagy in stromal cell-derived factor-1α (SDF-1α)-mediated dental pulp stem cell (DPSC) migration and pulp regeneration, and identify its presence during pulp revascularisation of pulpectomised dog teeth with complete apical closure. In vitro studies showed that SDF-1α enhanced DPSCs migration and optimised focal adhesion formation and stress fibre assembly, which were accompanied by autophagy. Moreover, autophagy inhibitors significantly suppressed, whereas autophagy activator substantially augmented SDF-1α-stimulated DPSCs migration. Furthermore, after ectopic transplantation of tooth fragment/silk fibroin scaffold with DPSCs into nude mice, pulp-like tissues with vascularity, well-organised fibrous matrix formation, and new dentin deposition along the dentinal wall were generated in SDF-1α-loaded samples accompanied by autophagy. More importantly, in a pulp revascularisation model in situ, SDF-1α-loaded silk fibroin scaffolds improved the de novo ingrowth of pulp-like tissues in pulpectomised mature dog teeth, which correlated with the punctuated LC3 and Atg5 expressions, indicating autophagy. Our findings provide novel insights into the pulp regeneration mechanism, and SDF-1α shows promise for future clinical application in pulp revascularisation.     

Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation

Long non-coding RNAs (lncRNAs) play regulatory roles in cancers. LncRNA PTENP1 is a pseudogene of the tumor suppressor gene PTEN but its roles in hepatocellular carcinoma (HCC) have yet to be explored. Here we confirmed that PTENP1 and PTEN were downregulated in several HCC cells, thus we constructed Sleeping Beauty (SB)-based hybrid baculovirus (BV) vectors for sustained PTENP1 lncRNA expression. Co-transduction of HCC cells with the SB-BV vector expressing PTENP1 elevated the levels of PTENP1 and PTEN, which suppressed the oncogenic PI3K/AKT pathway, inhibited cell proliferation, migration/invasion as well as induced autophagy and apoptosis. The overexpressed PTENP1 decoyed oncomirs miR-17, miR-19b and miR-20a, which would otherwise target PTEN, PHLPP (a negative AKT regulator) and such autophagy genes as ULK1, ATG7 and p62, indicating that PTENP1 modulated the HCC cell behavior and gene networks by miRNA regulation. Injection of the PTENP1-expressing SB-BV vector into mice bearing HCC tumors effectively mitigated the tumor growth, suppressed intratumoral cell proliferation, elicited apoptosis, autophagy and inhibited angiogenesis. These data collectively unveiled the molecular mechanisms of how PTENP1 repressed the tumorigenic properties of HCC cells and demonstrated the potential of the SB-BV hybrid vector for PTENP1 lncRNA modulation and HCC therapy.     

细胞自噬与EGFR抑制剂在肿瘤治疗中的研究进展

表皮生长因子受体(EGFR)抑制剂是近些年来肿瘤治疗的新策略。然而,先天性或者获得性耐药问题成为其疗效的一大障碍。自噬,是一种细胞自我消化的过程,并与耐药具有相关性。EGFR的激活能够通过多种信号通路调节自噬过程。EGFR抑制剂能够诱导自噬,然而EGFR诱导自噬的这种特殊作用是双向的。一方面,自噬能够增强EGFR抑制剂的细胞毒性作用,从而成为一种细胞的保护措施;另一方面,EGFR抑制剂治疗后产生的高自噬水平同样能够导致细胞自吞噬性死亡,从而逃脱凋亡,当EGFR抑制剂与一种自噬诱导剂联合应用时可能会产生更显著的治疗作用。因此,调节自噬水平将成为提高肿瘤患者EGFR抑制剂治疗效果的可行之举。     

Autophagy induced by infectious hematopoietic necrosis virus inhibits intracellular viral replication and extracellular viral yields in epithelioma papulosum cyprini cell line

Infectious hematopoietic necrosis virus (IHNV) is a common pathogen that causes severe disease in the salmonid aquaculture industry. Recent work demonstrated that autophagy plays an important role in pathogen invasion by activating innate and adaptive immunity. This study investigated the relationship between IHNV and autophagy in epithelioma papulosum cyprini cells. The electron microscopy results show that IHNV infection can induce typical autophagosomes which are representative structures of autophagy activation. The punctate accumulation of green fluorescence-tagged microtubule-associate protein 1 light chain 3 (LC3) and the protein conversion from LC3-I to LC3-II were respectively confirmed by confocal fluorescence microscopy and western blotting. Furthermore, the effects of autophagy on IHNV replication were also clarified by altering the autophagy pathway. The results showed that rapamycin induced autophagy can inhibit both intracellular viral replication and extracellular viral yields, while autophagy inhibitor produced the opposite results. These findings demonstrated that autophagy plays an antiviral role during IHNV infection.     

Pancreatic cancers require autophagy for tumor growth

Macroautophagy (autophagy) is a regulated catabolic pathway to degrade cellular organelles and macromolecules. The role of autophagy in cancer is complex and may differ depending on tumor type or context. Here we show that pancreatic cancers have a distinct dependence on autophagy. Pancreatic cancer primary tumors and cell lines show elevated autophagy under basal conditions. Genetic or pharmacologic inhibition of autophagy leads to increased reactive oxygen species, elevated DNA damage, and a metabolic defect leading to decreased mitochondrial oxidative phosphorylation. Together, these ultimately result in significant growth suppression of pancreatic cancer cells in vitro. Most importantly, inhibition of autophagy by genetic means or chloroquine treatment leads to robust tumor regression and prolonged survival in pancreatic cancer xenografts and genetic mouse models. These results suggest that, unlike in other cancers where autophagy inhibition may synergize with chemotherapy or targeted agents by preventing the up-regulation of autophagy as a reactive survival mechanism, autophagy is actually required for tumorigenic growth of pancreatic cancers de novo, and drugs that inactivate this process may have a unique clinical utility in treating pancreatic cancers and other malignancies with a similar dependence on autophagy. As chloroquine and its derivatives are potent inhibitors of autophagy and have been used safely in human patients for decades for a variety of purposes, these results are immediately translatable to the treatment of pancreatic cancer patients, and provide a much needed, novel vantage point of attack.     

谷氨酸致原代培养皮层神经元损伤中自噬的激活

目的: 体外观察谷氨酸介导的神经元氧化性损伤中自噬的激活,以及抑制自噬对谷氨酸致神经元毒性损伤的保护作用。方法: 体外培养皮层神经元,给予谷氨酸以及自噬抑制剂3-甲基腺嘌呤干预,MTT法检测细胞活力,透射电镜观察自噬泡的产生,激光共聚焦显微镜观察自噬特异性蛋白LC3的表达。结果: 给予谷氨酸干预后皮层神经元细胞存活率下降,自噬体数目明显增加,自噬标志性蛋白LC3表达增加。给予3-甲基腺嘌呤后,神经元细胞存活率增加,细胞自噬水平下降。结论: 谷氨酸诱导的神经元毒性损伤中存在自噬相关性细胞死亡,抑制自噬可能对谷氨酸毒性损伤有抑制作用,自噬抑制剂3-甲基腺嘌呤具有一定的神经保护作用。     

自噬与固有免疫应答相互调节研究进展

自噬在细胞分化、肿瘤、炎症、免疫等多方面发挥关键作用.近年来,随着分子生物学、细胞生物学、免疫学等学科的发展,研究发现细胞自噬与固有免疫应答有着重要的相互调控作用.自噬是固有免疫的重要组成成分,可以通过溶酶体直接降解被自噬体包裹的病原体.自噬参与众多固有免疫信号的调控.固有免疫信号也诱导或抑制自噬.自噬在抗胞内病原体感染中发挥重要作用.     

FAM48A mediates compensatory autophagy induced by proteasome impairment

Maintaining protein homeostasis is central to cell survival. The ubiquitin–proteasome system and autophagy play pivotal roles in protein quality control through protein degradation. Activities of these degradative pathways are carefully orchestrated, and autophagy is up‐regulated during proteasome dysfunction for cellular homeostasis. However, the mechanism by which proteasome impairment induces compensatory autophagy has remained largely elusive. Here, we show that FAM48A mediates autophagy induction during proteasome inhibition. FAM48A is degraded by the proteasome and accumulates in cells by proteasome inhibition. Knockdown of FAM48A led to defective induction of autophagy during proteasome inhibition and accompanied by defective localization of Atg9 on recycling endosomes. Our results indicate that FAM48A is a kind of sensor that is required for compensatory autophagy induction upon proteasome impairment.