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Intricate Functions of Matrix Metalloproteinases in Physiological and Pathological Conditions
Author(s) -
Mittal Rahul,
Patel Amit P.,
Debs Luca H.,
Nguyen Desiree,
Patel Kunal,
Grati M'hamed,
Mittal Jeenu,
Yan Denise,
Chapagain Prem,
Liu Xue Zhong
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25430
Subject(s) - matrix metalloproteinase , extracellular matrix , zymogen , basement membrane , microbiology and biotechnology , metastasis , proteolytic enzymes , biology , cancer research , chemistry , cancer , enzyme , biochemistry , genetics
Matrix metalloproteinases (MMPs) are a diverse group of proteolytic enzymes and play an important role in the degradation and remodeling of the extracellular matrix (ECM). In normal physiological conditions, MMPs are usually minimally expressed. Despite their low expression, MMPs have been implicated in many cellular processes ranging from embryological development to apoptosis. The activity of MMPs is controlled at three different stages: (1) transcription; (2) zymogen activation; and (3) inhibition of active forms by tissue inhibitor metalloproteinases (TIMPs). They can collectively degrade any component of ECM and basement membrane, and their excessive activity has been linked to numerous pathologies mainly including, but not limited to, tumor invasion and metastasis. The lack of information about several MMPs and the steady stream of new discoveries suggest that there is much more to be studied in this field. In particular, there is a need for controlling their expression in disease states. Various studies over the past 30 years have found that each MMP has a specific mode of activation, action, and inhibition. Drugs specifically targeting individual MMPs could revolutionize the treatment of a great number of health conditions and tremendously reduce their burden. In this review article, we have summarized the recent advances in understanding the role of MMPs in physiological and pathological conditions. J. Cell. Physiol. 231: 2599–2621, 2016. © 2016 Wiley Periodicals, Inc.