Apotosis plays a central role in lung remodeling associated with ILD [26] . An important molecule in the events associated with epithelial cell apoptosis is TGF-β, which is overexpressed in ILD. Downstream events linked to upregulation of TGF-β include modifications in the expression of various components of the cell cycle machinery, mainly the cyclin-dependent kinases (CDK) system that plays an essential role in ensuring proper cell cycle progression. Recently, much work has been focused on the protein p21cip1, a member of the CDK inhibitor family. This protein promotes cell cycle arrest to apoptosis in cases of cellular DNA damage. Interestingly, upregulation of p21cip1 has been reported in the lung tissues of patients with pulmonary fibrosis, primarily in hyperplastic alveolar epithelial cells [27] The increased expression of p21cip1 can favour the process of epithelial cell apoptosis. Apoptotic cells can also produce TGF-β. A consequence would be the perpetuation of a vicious cycle with TGF-β promoting epithelial cell apoptosis, which in turn increases the local production of TGF-β.