WFDC2 and renal fibrosis: More recently, LeBleu VS et al. identified HE4 as a mediator of renal fibrosis, which was upregulated in human and mouse fibrotic kidneys, through its capability as a protease inhibitor to suppress the activity of multiple proteases, such as serine proteases and matrix metalloproteinases, especially by inhibiting their ability to degrade type I collagen [7].