Sepsis is a life-threatening condition that occurs in response to an infection leading to a systemic inflammatory response. Various studies and research have been conducted to understand the molecular pathways involved in sepsis and finding novel therapeutic targets. C-terminal Fibronectin, a glycoprotein found in the extracellular matrix, has recently gained attention as a potential biomarker and therapeutic in sepsis management. This article aims to provide an overview of C-terminal Fibronectin’s role in sepsis and discuss its potential as a diagnostic and therapeutic target.
Sepsis is a life-threatening condition caused by an overwhelming immune response to invading pathogenic bacteria and their toxins. It is considered a public health emergency, with a high mortality rate of up to 70%. The pathogenesis of sepsis involves inflammation, immune and tissue damage, and pathophysiological changes in multiple organs, leading to the complexity of the disease. Macrophages play a critical role in all phases of sepsis and affect immune homeostasis and inflammatory processes. Macrophage dysfunction is a major cause of sepsis-induced immunosuppression, where septic patients or animal models experience a state of unresponsiveness or response tolerance to microbial products in vitro. Fibronectin (FN) is a biomarker of sepsis that correlates with clinical improvement in patient outcomes. However, extracting FN in its high molecular weight form from donor plasma poses difficulties, raising the need to generate FN with only the functional domain using genetic engineering, which could lead to a safer and more effective treatment for sepsis.
This study aimed to evaluate the protective effects of recombinant C-terminal heparin-binding domain of fibronectin (rhFNHC-36) in a murine model of sepsis induced by cecal ligation and puncture (CLP). Mice were randomly divided into four groups, including unoperated control, sham operation, phosphate-buffered saline control, and rhFNHC-36 treatment group. The mice in the control groups underwent either no procedure or a sham operation, while the mice in the experimental groups underwent CLP and were treated with either PBS or rhFNHC-36 at a dose of 40 mg/kg body weight via intravenous tail injection at three time points after surgery.
The study found that rhFNHC-36 exhibited beneficial effects in bacterial clearance, organ atrophy, tissue damage, and dysregulated inflammation during sepsis. Moreover, the mechanisms of action of rhFNHC-36 in modulating macrophage activities were explored. The results showed that rhFNHC-36 significantly attenuated macrophage dysfunction and upregulated the expression of immune surface markers, such as major histocompatibility complex class II and CD40. Besides, rhFNHC-36 inhibited the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6, and contributed to the resolution of inflammation during sepsis.
In conclusion, the study provides evidence on the potential therapeutic value of rhFNHC-36 in sepsis treatment by improving macrophage functions and reducing inflammation. The findings also highlight the importance of genetic engineering in generating therapeutic proteins with only the functional domain, which could lead to safer and more effective treatments for sepsis and other conditions. Since sepsis remains a significant health issue globally, this research provides an important contribution to the understanding and treatment of this complex and potentially fatal condition.
In conclusion, understanding the role of C-terminal Fibronectin in sepsis can greatly impact future diagnosis and treatment options for patients. By identifying the specific markers of sepsis and developing treatments that target C-terminal Fibronectin, we can improve patient outcomes and save lives. More research is necessary to fully understand the mechanisms behind this protein’s involvement in sepsis, but the discoveries made thus far are promising. As we continue to explore the complex nature of sepsis, we must recognize the importance of C-terminal Fibronectin and its potential as a critical tool in the fight against this deadly condition.
