WFDC2 and Interstitial cardiac fibrosis: During the cardiac fibrosis in dilated cardiomyopathy, HE4 functions as a secretory factor, activating cardiac fibroblasts, thereby inducing cardiac interstitial fibrosis [25]. In kidney fibrosis, HE4 was confirmed to inhibit the capacity to degrade type I collagen by targeting two serine proteases, Prss35 and Prss23 [45].