title: Klotho Regulates Cigarette Smoke-Induced Autophagy: Implication in Pathogenesis of COPD.
abstract: Chronic obstructive pulmonary disease is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a fundamental cellular process that eliminates long-lived proteins and damaged organelles through lysosomal degradation pathway, though its role in human diseases remains unclear. We hypothesized that an anti-aging protein, Klotho plays an important role in regulating autophagy in response to cigarette smoke (CS).
  
  
  
  Autophagy was measured by detecting LC3-I and LC3-II expressions. The regulation of autophagy expression by cigarette smoke extract (CSE) was studied in vitro, and small-interfering RNA (siRNA) and recombinant Klotho were employed to investigate the role of Klotho on CSE-induced autophagy. Protein levels and phosphorylation were measured by Western blot assay.
  
  
  
  CS exposure resulted in induction of autophagy in alveolar macrophages. Pretreatment of cells with Klotho attenuated CS-induced autophagy whereas knockdown of Klotho augmented CS-induced autophagy. Klotho inhibited phosphorylation of ERK, Akt, and IGF-1 in CSE-stimulated cells.
  
  
  
  These data suggest that Klotho plays a critical role in the regulation of CS-induced autophagy and have important implications in understanding the mechanisms of CS-induced cell death and senescence.
authors.affiliation: Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, China. illl1210@126.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Emergency, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Tu
authors.affiliation: Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, China. sduzhiwei@sina.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D000073865:Cigarette Smoking / Q000009:adverse effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000090265:Klotho Proteins; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D014162:Transfection
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D012906:Smoke; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Alveolar macrophages; Anti-aging protein; CSE; Senescence