This progression can be reduced by suppression of Htra1. It is vigilance that cerulein induced pancreatic ADM in KC mice progression to high grade of PanIN lesions, and even partial progression to PDAC with the upregulation of Htra1, but pancreatitis-initiated PDAC after Htra1 overexpression can be reversed by CDK1 inhibitor (Fig. 7d, e). This evidence concerns the gene HTRA1 and keratoconus.