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CTSG
CTSG Full Name
cathepsin G
CTSG Introduction
Cathepsin G (CTSG) is a critical serine protease belonging to the S1 peptidase family within the chymotrypsin superfamily. The product of the CTSG gene is a 255-amino acid precursor protein (preproCatG), which undergoes a series of post-translational modifications and processing to eventually form the mature active protein with a molecular weight of approximately 28–35 kDa. Its catalytic activity relies on a classic catalytic triad composed of His, Asp, and Ser residues, which form the core of its proteolytic function. In terms of subcellular localization, CTSG is primarily stored in the primary granules—specifically the azurophil granules—of neutrophils. CTSG exhibits a rare dual substrate specificity: it possesses chymotrypsin-like activity, capable of cleaving peptide bonds at the carboxyl side of large hydrophobic or aromatic amino acid residues (such as phenylalanine), as well as trypsin-like activity, enabling it to recognize and cleave peptide bonds following basic amino acids (such as lysine and arginine). This broader substrate spectrum compared to most chymotrypsins allows CTSG to degrade a variety of extracellular matrix proteins and plasma proteins.
Figure 1. Three-dimensional structure of human CTSG. (Source: Burster T, et al. 2020)
Under physiological conditions, when neutrophils are activated and arrive at sites of infection or injury, they release CTSG extracellularly through degranulation. Released CTSG can directly kill invading pathogens such as bacteria and fungi, exerting a direct antimicrobial effect. More importantly, through its proteolytic activity, CTSG finely "edits" and "remodels" the immune microenvironment. It cleaves and modifies a variety of signaling molecules, including cytokines, chemokines, and their receptors, thereby regulating the recruitment, activation, and function of immune cells. For example, CTSG can process and activate precursor forms of inflammatory mediators, such as converting pro-IL-1β and TNF-α into their active forms, amplifying local inflammatory signals. It can also alter cellular responsiveness by cleaving cell surface receptors and can increase vascular permeability, facilitating the entry of more immune cells into inflamed tissues. Additionally, CTSG plays a role in antigen presentation and the initiation of adaptive immunity. Its influence on MHC class I molecules may exhibit dual effects, highlighting its potential role in bridging innate and adaptive immunity.
However, CTSG functions as a double-edged sword. When its activity becomes dysregulated or its expression is abnormal, its potent proteolytic capability shifts from host defense to a driver of tissue damage. Uncontrolled CTSG activity leads to excessive degradation of the extracellular matrix, disruption of basement membranes, and cellular injury. Given its strong pro-inflammatory and tissue-destructive potential, CTSG plays a significant role in the pathogenesis of various acute and chronic inflammatory diseases and autoimmune disorders. In these diseases, excessive neutrophil activation or aberrant cell death leads to massive release of CTSG, exacerbating pathological damage. In rheumatoid arthritis (RA), CTSG is considered one of the key factors in joint destruction. It directly contributes to the loss of cartilage matrix by degrading proteoglycans and collagen within articular cartilage. Simultaneously, it activates synovial cells and immune cells, triggering the release of more inflammatory factors and creating a self-amplifying vicious cycle. The role of CTSG is also prominent in respiratory diseases. In acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), massive neutrophil infiltration in the lungs results in the release of CTSG, which disrupts the integrity of the alveolar-capillary barrier, leading to pulmonary edema and impaired gas exchange.
Alternate Names for CTSG
CTSG; cathepsin G; CG; CATG;
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