Gelatinase B (, ''92-kDa gelatinase'', ''matrix metalloproteinase 9'', ''type V collagenase'', ''92-kDa type IV collagenase'', ''macrophage gelatinase'', ''95 kDa type IV collagenase/gelatinase'', ''collagenase IV'', ''collagenase type IV'', ''gelatinase MMP 9'', ''MMP 9'', ''type IV collagen metalloproteinase'') is an enzyme. This enzyme catalyses the following chemical reaction : Cleavage of gelatin types I and V and

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

types IV and V This enzyme is similar to

gelatinase A Gelatinase A, also known as MMP2 (, ''72-kDa gelatinase'', ''matrix metalloproteinase 2'', ''type IV collagenase'', ''3/4 collagenase'', ''matrix metalloproteinase 5'', ''72 kDa gelatinase type A'', ''collagenase IV'', ''collagenase type IV'', ''MM ...

, but possesses a further domain. Regarding its structure, Gelatinase B has domains which can bind with gelatin, laminin, and collagens type I and IV- collagenases do not possess these binding domains.

Function

Due to its role in cleaving

in the extracellular matrix, gelatinase B has multiple functional roles in normal physiology.

Neutrophil action

Gelatinase B, along with elastase, appears to be a regulatory factor in neutrophil migration across the

basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...

. Gelatinase B plays several important functions within neutrophil action, such as degrading extracellular matrix, activation of IL-1β, and cleavage of several chemokines. In a mouse model, Gelatinase B deficiency resulted in resistance to endotoxin shock, suggesting that Gelatinase B is important in sepsis.

Angiogenesis

Gelatinase B may play an important role in

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

and neovascularization. For example, gelatinase B appears to be involved in the remodeling associated with malignant glioma neovascularization. It is also a key regulator of growth plate formation—both growth plate angiogenesis and the generation of hypertrophic

chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteog ...

s. Knock-out models of Gelatinase B result in delayed

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

, vascularization, and ossification of hypertrophic chondrocytes. Lastly, there is significant evidence that Gelatinase B is required for the recruitment of

endothelial stem cell Endothelial stem cells (ESCs) are one of three types of stem cells found in bone marrow. They are multipotent, which describes the ability to give rise to many cell types, whereas a pluripotent stem cell can give rise to all types. ESCs have t ...

s, a critical component of angiogenesis

Wound repair

In in vitro experiments, it has been demonstrated that gelatinase B is greatly upregulated during human respiratory epithelial healing. Using a gelatinase B deficient mouse model, it was seen that gelatinase B coordinated epithelial wound repair and deficient mice were unable to remove the fibrinogen matrix during wound healing. When interacting with TGF-ß1, Gelatinase B also stimulates collagen contraction, aiding in wound closure.

Pathology

Gelatinase B has been found to be associated with numerous pathological processes, including immunologic and vascular diseases. For example, it has been implicated in the development of

aortic aneurysm An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. They usually cause no symptoms except when ruptured. Occasionally, there may be abdominal, back, or leg pain. The prevalence of abdominal aortic ...

s, and its disruption prevents the development of aortic aneurysms. Elevated gelatinase B levels can also be found in the cases of rheumatoid arthritis and focal brain

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

. However, one of its most widely studied associated pathology is the relationship between Gelatinase B and cancer, due to its role in extracellular matrix remodeling and angiogenesis. For example, its increased expression was seen in a metastatic mammary cancer cell line. A.R. Farina and others have argued that Gelatinase B plays a central role in tumor progression, from angiogenesis, to stromal remodeling, and ultimately metastasis. However, because of its physiologic function, it may be difficult to leverage Gelatinase B inhibition into cancer therapy modalities. However, Gelatinase B has been investigated in tumor metastasis diagnosis—complexes of Gelatinase B/Tissue Inhibitors of Metalloproteinases are seen to be increased in gastrointestinal cancer and gynecologic malignancies

References

External links

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