A subsequent study using immunofluorescence demonstrated that human COPD bronchial tissue has enhanced NICD1 (Notch1 intercellular domain) and HEY2 (hairy/enhancer-of-split related with YRPW motif protein 2) (both key in Notch signal transduction) in areas of goblet cell metaplasia in the airway epithelium and submucosal glands [80]. This evidence concerns the gene NOTCH1 and chronic obstructive pulmonary disease.