Plg, plasminogen, is the zymogen of plasmin, a major enzyme degrading fibrin clots. It plays a crucial role in fibrinolysis and is involved in cell migration as its activation on cell surfaces promotes proteolytic activity. Plg also participates in various physiological processes like inflammation resolution and lactation [1,2,3,5]. Genetic models such as gene knockout mice have been instrumental in studying its functions.

Plg -/- and Plg -RKT -/- mice showed decreased mononuclear cell recruitment to the pleural cavity in a murine pleurisy model, with associated decreased CCL2 levels in pleural exudates. These mice also had increased percentages of M1-like macrophages, and defective M2-like polarization was observed in bone-marrow-derived macrophages. Additionally, phagocytosis of apoptotic neutrophils was reduced in these mice, suggesting Plg and Plg-RKT regulate macrophage polarization and efferocytosis in inflammation resolution [5]. Plg-RKT-deficient mice fed a high-fat diet gained more weight, developed more hepatic steatosis, and were more insulin-resistant/glucose-intolerant, indicating its role in adipose function and metabolic homeostasis [4].

In conclusion, Plg, through its receptor Plg-RKT, is essential for processes like inflammation resolution and metabolic regulation. Gene knockout mouse models have revealed its significance in these biological processes, offering insights into potential mechanisms underlying related diseases such as inflammation-associated disorders and metabolic diseases [4,5].

References:

1. Miles, Lindsey A, Vago, Juliana P, Sousa, Lirlândia P, Parmer, Robert J. 2020. Functions of the plasminogen receptor Plg-RKT. In Journal of thrombosis and haemostasis : JTH, 18, 2468-2481. doi:10.1111/jth.15014. https://pubmed.ncbi.nlm.nih.gov/32662180/

2. Miles, Lindsey A, Lighvani, Shahrzad, Baik, Nagyung, Mueller, Barbara M, Parmer, Robert J. . New insights into the role of Plg-RKT in macrophage recruitment. In International review of cell and molecular biology, 309, 259-302. doi:10.1016/B978-0-12-800255-1.00005-3. https://pubmed.ncbi.nlm.nih.gov/24529725/

3. Lee, Beomki, Kim, Suekyeung, Lee, Jae Joon, Kim, Duk-Kyung, Kim, Hee-Jin. . Severe dysplasminogenemia due to homozygous PLG Ala620Thr variant in a Korean woman without a history of venous thromboembolism: A case report and literature review. In Medicine, 101, e29013. doi:10.1097/MD.0000000000029013. https://pubmed.ncbi.nlm.nih.gov/35244080/

4. Samad, Fahumiya, Bai, Hongdong, Baik, Nagyung, Parmer, Robert J, Miles, Lindsey A. 2021. The plasminogen receptor Plg-RKT regulates adipose function and metabolic homeostasis. In Journal of thrombosis and haemostasis : JTH, 20, 742-754. doi:10.1111/jth.15622. https://pubmed.ncbi.nlm.nih.gov/34897983/

5. Vago, Juliana P, Sugimoto, Michelle A, Lima, Kátia M, Miles, Lindsey A, Sousa, Lirlândia P. 2019. Plasminogen and the Plasminogen Receptor, Plg-RKT, Regulate Macrophage Phenotypic, and Functional Changes. In Frontiers in immunology, 10, 1458. doi:10.3389/fimmu.2019.01458. https://pubmed.ncbi.nlm.nih.gov/31316511/