Dental Pulp Stem Cell-Derived Exosomes Inhibit Senescence-Induced Chronic Obstructive Pulmonary Disease Through the Nuclear Factor Kappa B Signaling Pathway

Abstract

The respiratory condition known as chronic obstructive pulmonary disease (COPD) is widespread, but its pathogenesis remains unclear. To investigate the mechanism by which dental pulp stem cells (DPSCs) and their exosomes inhibit cellular senescence, senescence was first induced in bronchial epithelial cells by treatment with 5% cigarette smoke extract (5% CSE). Our results revealed that the senescence of bronchial epithelial cells induced by 5% CSE was decreased when co-cultured with dental pulp stem cells or their exosomes. Furthermore, this study identified that 5% CSE promoted cell senescence through the Nuclear factor kappa B (NF-kB) pathway. In addition, 5% CSE-induced cell senescence was limited when IKKβ was knocked out in bronchial epithelial cells. Meanwhile, DPSCs inhibited cell senescence through exosomal-MALAT1. Contrastingly, this effect was reversed by MALAT1 knockout. In the mouse COPD model, it was found that DPSCs could effectively inhibit COPD progression via reducing cell senescence-related proteins in mouse lung tissues, such as p21 and GLB1, and upregulating the MALAT1 expression. TNF-α and p21 expression levels were considerably reduced after treatment with dental pulp stem cells, according to IHC staining. Finally, we validated that DPSCs and their exosomes inhibit cell senescence by regulating MALAT1 and the NF-kB pathway in vitro as well as in vivo, thereby exerting a therapeutic effect in COPD.