MMP9-Matrix Metalloproteinase 9 |Elisa - Clia - Antibody - Protein

Background:

Matrix metalloproteinase 9 (MMP-9), also known as gelatinase B, is an enzyme belonging to the matrix metalloproteinase family. MMP-9 is a zinc-dependent endopeptidase. It is synthesized as a proenzyme, and requires activation by other proteases to become active. The active form of MMP-9 can degrade various components of the extracellular matrix, including collagen type IV, which is a major component of the basement membrane. MMP-9 is implicated in several physiological and pathological processes, including tissue remodeling, angiogenesis, wound healing, inflammation, and cancer metastasis. It is involved in the breakdown of the extracellular matrix, which is essential for processes like tissue repair and remodeling. However, dysregulation of MMP-9 activity can contribute to pathological conditions such as excessive tissue degradation, tumor invasion, and metastasis.MMP-9 activity is tightly regulated at multiple levels, including transcriptional regulation, post-translational modification, and inhibition by tissue inhibitors of metalloproteinases (TIMPs). Various signaling pathways and factors such as growth factors, cytokines, and inflammatory mediators can modulate the expression and activity of MMP-9 in different cell types and tissues. MMP-9 has been implicated in numerous diseases and pathological conditions, including cancer, cardiovascular diseases, neurological disorders, inflammatory diseases, and connective tissue disorders. Elevated levels of MMP-9 have been observed in the serum, tissues, and biological fluids of patients with these conditions, making it a potential biomarker for disease diagnosis, prognosis, and therapeutic target.

Protein Structure:

MMP9 is a zinc-dependent endopeptidase composed of several domains:

• Signal Peptide: Directs the enzyme to the secretory pathway.
• Propeptide Domain: Maintains the enzyme in an inactive form until cleaved.
• Catalytic Domain: Contains the zinc-binding motif essential for its proteolytic activity.
• Hemopexin-like Domain: Involved in substrate specificity and interaction with tissue inhibitors of metalloproteinases (TIMPs).
• Fibronectin Type II Modules: Important for binding to gelatin and collagen.

Classification and Subtypes:

MMP9 is classified within the MMP family based on its structural features and substrate specificity. Within this family, MMP9 is categorized under the gelatinases, alongside MMP2 (gelatinase A).

Function and Biological Significance:

MMP9 has several critical biological functions:

• Extracellular Matrix Degradation: MMP9 degrades major components of the ECM, such as type IV and V collagens and gelatin, facilitating tissue remodeling.
• Cell Migration: By remodeling the ECM, MMP9 allows for cell migration, which is crucial during processes such as angiogenesis, wound healing, and immune cell trafficking.
• Inflammation: MMP9 modulates the inflammatory response by processing cytokines and chemokines, influencing immune cell recruitment.
• Tumor Progression: MMP9 promotes tumor invasion and metastasis by degrading ECM barriers and enabling cancer cell dissemination.

Interactions:

• Substrates: MMP9 acts on various ECM proteins, including collagens, elastin, and proteoglycans.
• Tissue Inhibitors of Metalloproteinases (TIMPs): TIMPs, particularly TIMP-1, regulate MMP9 activity by forming inhibitory complexes.
• Integrins: MMP9 interacts with integrins on the cell surface, influencing cell-ECM interactions and signaling pathways.
• Growth Factors: MMP9 can release and activate growth factors such as vascular endothelial growth factor (VEGF), promoting angiogenesis.

Clinical Issues:

• Cancer: Elevated levels of MMP9 are associated with tumor aggressiveness, metastasis, and poor prognosis in various cancers, including breast, lung, and colorectal cancers.
• Cardiovascular Diseases: MMP9 contributes to the pathogenesis of atherosclerosis, myocardial infarction, and aneurysm formation by degrading ECM components and modulating inflammatory responses.
• Inflammatory Diseases: MMP9 is implicated in chronic inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease, where it mediates tissue destruction and remodeling.

Summary:

MMP9 is a crucial enzyme involved in the degradation of the extracellular matrix, with significant roles in physiological and pathological processes. Its ability to modulate ECM components, cell migration, and inflammatory responses underscores its importance in tissue remodeling and disease progression. In cancer, MMP9 facilitates tumor invasion and metastasis, making it a potential target for therapeutic intervention. Understanding the regulation and function of MMP9 in various diseases can lead to the development of novel diagnostic and therapeutic strategies.