MMP9

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ProMMP9

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MMP9-probe 4JIJ

Matrix metallopeptidase 9 (MMP-9), also known as gelatinase B, is an enzyme that in humans is encoded by the MMP9 gene. MMP-9 is part of the matrix metalloproteinase (MMP) family, a diverse group of peptidases involved in the breakdown of the extracellular matrix (ECM) in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. MMP-9 specifically degrades the components of the basement membrane, a critical step in the process of cancer cell metastasis and angiogenesis.

Function

MMP-9 plays a crucial role in the breakdown of extracellular matrix in various physiological and pathological processes. It is capable of degrading a variety of substrates including collagen types IV and V, gelatin, and fibronectin, making it a key player in tissue remodeling and repair. MMP-9 is secreted as a zymogen (pro-MMP-9) and requires activation to become fully functional. This activation can be mediated by other MMPs or by plasmin.

Regulation

The activity of MMP-9 is regulated at multiple levels, including transcription, zymogen activation, and inhibition by tissue inhibitors of metalloproteinases (TIMPs). The expression of MMP-9 is induced by various growth factors, cytokines, and chemokines, and is tightly controlled by transcription factors such as AP-1 and NF-κB. The balance between MMP-9 and its inhibitors, particularly TIMP-1, is critical for maintaining tissue homeostasis.

Clinical Significance

MMP-9 has been implicated in a variety of diseases due to its role in ECM degradation. Its overexpression is associated with cancer, arthritis, cardiovascular diseases, and neurological disorders. In cancer, MMP-9 facilitates tumor growth and metastasis by degrading the basement membrane and extracellular matrix, allowing cancer cells to invade neighboring tissues and spread to distant organs. In arthritis, the excessive breakdown of cartilage by MMP-9 contributes to joint destruction. MMP-9 is also involved in the pathological processes of cardiovascular diseases, such as atherosclerosis, by contributing to the remodeling of blood vessels.

Therapeutic Target

Given its role in various diseases, MMP-9 has been explored as a therapeutic target. Inhibitors of MMP-9 have been developed in an attempt to block its activity and slow down the progression of diseases such as cancer and arthritis. However, the clinical use of MMP-9 inhibitors has been challenging due to the broad functions of MMPs in normal physiological processes and the potential for side effects.

See Also

• Matrix metalloproteinase
• Extracellular matrix
• Tissue inhibitor of metalloproteinases
• Cancer metastasis
• Angiogenesis