Adrenomedullin regulates club cell recovery following lung epithelial injury

Abstract

The equilibrium between lung epithelium damage and recovery in the context of chronic injury is at the basis of numerous lung diseases, including lung cancer and COPD. Understanding the contribution of growth factors and other molecular intermediates to this crosstalk may help in devising new therapeutic approaches. To better understand the contribution of adrenomedullin (AM) to lung homeostasis, we built club cell-specific conditional knockout (KO) mice for AM and subjected them to naphthalene injury. Untreated KO mice had lower levels of club cell 10 KDa protein (CC10) immunoreactivity than their wild type (WT) littermates in both terminal and regular bronchioles. Naphthalene injury resulted in a rapid necrosis of club cells followed by a progressive recovery of the epithelium. Club cells proliferated at higher rates in the KO mice and at 21 days post-injury the club cell coverage of the main bronchioles was higher and more homogeneous than in the WT animals. In conclusion, the paracrine/autocrine influence of AM in club cells subtly modulates their proliferation and spreading kinetics during lung epithelium recovery.