**Matrix Metalloproteinases in Asthma-Associated Airway Remodeling – Dr. Jekyll or Mr. Hyde ?**

Katarzyna Grzela, Agnieszka Strzelak, Wioletta Zagórska and Tomasz Grzela

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/62440

#### **Abstract**

Matrix metalloproteinases (MMPs) are Zn2+-dependent endoproteases, which digest extracellular matrix (ECM) components and various non-ECM molecules. Main physiological role of MMPs concerns regulation of tissue remodeling and regenera‐ tion. The production and activity of MMPs are tightly supervised by multistage control mechanisms. These mechanisms include regulation of gene expression, and various post-transcriptional/post-translational modifications. However, without proper control MMPs reveal dual nature, similarly to character from the novella by R.L. Stevenson, "Strange Case of Dr Jekyll and Mr Hyde". They become dangerous molecules, involved in cancer metastasis, or cardiovascular diseases.

Recent studies revealed that MMPs are also engaged in asthma. Despite extensive research, exact role of MMPs in this process remains unclear and there is no agree‐ ment among scientists, regarding two opposite concepts. The followers of "destruc‐ tive hypothesis" postulate detrimental effect of MMPs on mucosa. Accordingly, MMPsmediated damage stimulates chaotic regeneration, and progressive remodeling. Oppositely, enthusiasts of "protective hypothesis" postulate that MMPs actually do not allow formation of excessive collagen deposits, and thus they protect from tissue fibrosis.

The better understanding of "MMPs — Jekyll or Hyde ?" story may be clinically relevant, especially while considering therapies focused on modulation of MMPs activity. Therefore, this issue requires instant elucidation.

**Keywords:** airway remodeling, asthma, extracellular matrix, matrix metalloprotei‐ nase, destructive hypothesis and protective hypothesis

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **1. Introduction**

Matrix metalloproteinases (MMPs) represent group of 25 endoproteases, which require a presence of zinc ions to reveal their proteolytic activity. According to worldwide accepted nomenclature, MMPs have assigned numbers from 1 to 28. However, till now no respective molecules have been ascribed for numbers 4, 5 and 6, whereas MMP-18 was identified only in *Xenopus* frogs. [1, 2] Apart from regulation of extracellular matrix (ECM) turnover, MMPs are also involved in controlling of numerous non-ECM molecules, including cytokines and growth factors. Thus, MMPs are key molecules in embryo- and organogenesis, angiogenesis and tissue regeneration. However, they are also main destructive factors, responsible for cancer progres‐ sion, aortic aneurysm rupture or delayed healing of chronic wounds. [3, 4] Recently, their involvement was postulated also in some inflammatory diseases affecting respiratory tract, among them chronic obstructive pulmonary disease and asthma. [5] In this chapter authors will focus especially on possible role of MMPs in asthma and asthma-associated alterations in architecture and function of respiratory tract mucosa, which are better known as airway remodeling.
