title: Soluble extracellular Klotho decreases sensitivity to cigarette smoke induced cell death in human lung epithelial cells.
abstract: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the US and is associated with an abnormal inflammatory response to cigarette smoke (CS). Exposure to CS induces oxidative stress and can result in cellular senescence in the lung. Cellular senescence can then lead to decreased proliferation of epithelial cells, the destruction of alveolar structure and pulmonary emphysema. The anti-aging gene, klotho, encodes a membrane bound protein that has been shown to be a key regulator of oxidative stress and cellular senescence. In this study the role of Klotho (KL) with regard to oxidative stress and cellular senescence was investigated in human pulmonary epithelial cells exposed to cigarette smoke. Individual clones that stably overexpress Klotho were generated through retroviral transfection and geneticin selection. Klotho overexpression was confirmed through RT-qPCR, Western blotting and ELISA. Compared to control cells, constitutive Klotho overexpression resulted in decreased sensitivity to cigarette smoke induced cell death in vitro via a reduction of reactive oxygen species and a decrease in the expression of p21. Our results suggest that increasing Klotho level in pulmonary epithelial cells may be a promising strategy to reduce cellular senescence and mitigate the risk for the development of COPD.
authors.affiliation: Department of Biology, Fort Lewis College, 1000 Rim Drive, Durango, CO 81301, United States. Electronic address: blake_d@fortlewis.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Blake
authors.affiliation: Department of Biology, Fort Lewis College, 1000 Rim Drive, Durango, CO 81301, United States.
authors.forename: Caitlyn M
authors.initials: CM
authors.lastname: Reese
authors.affiliation: Department of Biology, Fort Lewis College, 1000 Rim Drive, Durango, CO 81301, United States.
authors.forename: Mario
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Department of Biology, Fort Lewis College, 1000 Rim Drive, Durango, CO 81301, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Dahlmann
authors.affiliation: Department of Biology, Fort Lewis College, 1000 Rim Drive, Durango, CO 81301, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dean
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D000090265:Klotho Proteins; D008168:Lung / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012995:Solubility; D014026:Nicotiana
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D012906:Smoke; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Aging; COPD; Cigarette smoke; Epithelial cells; Klotho; Oxidative stress