Progressive loss of organ function in most organs is associated with
fibrosis, a tissue state associated with abnormal matrix buildup. If highly progressive, the fibrotic process eventually leads to organ failure and death.
Fibrosis is a basic connective tissue lesion defined by the increase in the amount of fibrillar extracellular matrix (ECM) components in a tissue or organ. In addition, intrinsic changes in important structural cells can induce the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix-producing myofibroblasts. ECM
enzymes belonging to the family of
matrix metalloproteinases (
MMPs) and lysyl
oxidases (LOXs) play a crucial role in ECM remodeling and regeneration.
MMPs have a catalytic role in degradation of ECM, whereas LOX/LOXLs mediate ECM, especially
collagen, cross-linking and stiffening. Importantly,
enzymes from both families are elevated during the fibrotic response to tissue injury and its resolution. Yet, the apparent molecular competition or antagonistic activities of these
enzyme families during the various stages of
fibrosis is often overlooked. In this review, we discuss the diverse roles of
MMPs and LOX/LOXL2 in chronic organ
fibrosis. Finally, we review contemporary therapeutic strategies for
fibrosis treatment, based on neutralization of
MMP and LOX activity, as well as the development of novel drug delivery approaches.