Fig. 2
From: Cell mediated ECM-degradation as an emerging tool for anti-fibrotic strategy
Mechanism of ECM degradation. A Mechanism of collagen degradation. Extracellular collagen degradation pathway: The triple helix structure of the collagen fibrils is unwound by collagenases (including MMP1, MMP8, MMP13, cathepsin K, etc.). Collagen fibrils are cleaved by these collagenases and then further degraded by gelatinases (i.e., MMP2 and MMP9). Intracellular collagen degradation pathway: During phagocytosis, uptake of collagen fibrils is mediated by the β1-integrin family and the actin-rich pseudopods. Macropinocytosis involves the uptake of collagen fragments mediated by actin. In endocytosis, collagen is recognized by the uPARAP/Endo180 receptors and subsequently taken up by clathrin-mediated vesicles. The ingested collagen is further degraded by cysteine proteases in the lysosomes. B Mechanism of elastin degradation. Elastin can be degraded by metalloproteinases (MMP2, MMP7, MMP9, MMP12, MMP14 and neprilysin), serine proteinases (Ela-2, CatG, PR-3 and Chymotrypsin-like elastase 1), and cysteine proteinases (cathepsin B, F, K, L, V and S). C Mechanism of HA degradation. HA with high molecular weight is first degraded into fragments of approximately 20 kDa by HYAL2, which is then recognized by CD44 and internalized. Finally, the fragment is completely degraded by β-glucuronidase, β-N-acetyl glucosaminidase, and HYAL1 in the lysosome