This protein plays a central role in cell senescence, mainly by inducing the dephosphorylation of the cyclin-dependent kinase inhibitor p21 and by activating the cell cycle inhibitor retinoblastoma [49]. following administration of 3 concentrations of CAE (50 g/mL, 100 g/mL, and 200 g/mL) to A549 cells. Results CAE inhibited senescence in ARD-induced A549 cells. It inhibited p16, p21, p53, and a senescence-associated secretory phenotype, and reduced expression of the senescence-related positive cells of -galactosidase. Further study revealed that activation of the -catenin signaling pathway is closely associated with p53. CAE inhibited senescence in A549 cells via the -catenin/p53 pathway. Further, inhibition of -catenin was associated with reduced expression levels of p53 and p21, and the anti-aging effects of CAE were enhanced. When expression of p53 was inhibited, expression levels of -catenin also tended to decrease. Conclusions In summary, our study showed that CAE can inhibit aging in A549 cells to alleviate pulmonary fibrosis, and thus limit the secretion of the extracellular matrix and collagen in lung fibroblasts. strong class=”kwd-title” Keywords: beta Catenin, Cell Aging, Tumor Suppressor Protein p53 Background Idiopathic pulmonary fibrosis (IPF) is a gradual, irreversible, and serious disease of unknown origin, which occurs predominantly in elderly individuals [1]. Primary NS-2028 manifestations include fibrosis and honeycomb-like changes in the subpleural and basal regions of the lungs and deposition of collagen and extracellular matrix (ECM) around the NS-2028 pulmonary fibrosis foci [2]. Gradual loss of lung function and increased fatigability are associated with disease progression. Histopathological findings show patterns similar to interstitial pneumonia, which is characterized by patchy involvement of distal airways and lung parenchyma, with areas of alveolar damage and fibrotic remodeling [3]. With the increase of the elderly population in the past 10 years, the incidence rate of IPF has increased correspondingly [4]. Epidemiological and clinical data indicate that IPF is a disease related to aging and is prevalent in elderly individuals. Further, the incidence and mortality rates of IPF increase Rabbit Polyclonal to Patched with age [5]. The main pathogenesis of pulmonary fibrosis NS-2028 involves the damage of type II alveolar epithelial cells (AEC IIs), which releases a large number of inflammatory factors that activate lung fibroblasts and induces the secretion of large quantities of ECM [6,7], eventually leading to lung scarring and remodeling. Studies have shown that aging is a key factor that affects the initiation and development of IPF, in which AEC IIs senescence is definitely closely related to the event and development of pulmonary fibrosis [8]. Mechanisms involved in IPF disease development and progression include repeated injury to the lung epithelium, activation and proliferation of myofibroblasts, and modified production of ECM, collectively resulting in the damage of lung architecture and function [9,10]. Epidemiological investigations have shown that IPF primarily happens in individuals over 60 years of age. Indeed, accumulating evidence suggests that the induction of cellular senescence may play an important part in the pathogenesis of radiation-induced pulmonary fibrosis and additional fibrotic lung diseases, including IPF and pulmonary fibrosis induced by bleomycin [11]. Senescent AEC IIs have been recognized in fibrotic foci in the lungs of individuals with IPF. Similarly, mice treated with bleomycin or thoracic irradiation demonstrate raises in senescent AEC IIs, the putative alveolar stem cells (ASCs) [12]. When AEC IIs/ASCs become senescent, they cannot self-renew and generate AEC to keep up the homeostasis of the alveolar epithelium and restoration the epithelium after cells injury; however, they continue to occupy the stem cell market. In addition, senescent AEC II can set in motion a self-perpetuating vicious cycle of an irregular tissue restoration process and secondary senescence by initiating oxidative stress and inflammation. This in turn prospects to the disruption of normal cells structure and function, in part via reactive oxygen species and the senescence-associated secretory NS-2028 phenotype (SASP), which eventually prospects to pulmonary fibrosis [13]. Cellular senescence is definitely regulated by complex.