SERPINE1 gene

The SERPINE1 gene (SERPINE1 stands for: Serpin Family E Member 1) is a protein-coding gene located on chromosome 7q22.1. An important paralog of this gene is SERPINE2.

The SERPINE1 gene encodes a member of the serine proteinase inhibitor superfamily (serpine 1). This member is the most important inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA) and thus an inhibitor of fibrinolysis. The protein Serpine1, encoded by the SERPINE1 gene, also functions as a component of innate antiviral immunity. Defects in SERPINE1 are the cause of plasminogen activator inhibitor 1 deficiency (PAI-1 deficiency). High levels of the gene product are associated with thrombophilia.

Serpine1 as a serine protease inhibitor is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As a PLAT inhibitor, it is required for the down-regulation of fibrinolysis and is responsible for the controlled breakdown of blood clots. As a PLAU inhibitor, it is involved in the regulation of cell adhesion and proliferation.

Serpine1 acts as a regulator of cell migration, independent of its role as a protease inhibitor (Szabo R et al. 2005). It is required for the stimulation of keratinocyte migration during skin injury repair (Simone TM et al. 2014; Providence KM et al. 2008). Serpine1 is a downstream target of TGFbeta and acts as a chemotactic mediator for mast cells and induces the expression of intercellular adhesion molecule 1(ICAM1) in fibroblasts, which is required for mast cell adhesion to fibroblasts.

Serpine1 plays a role in the senescence of alveolar type 2 cells in the lung. The protease inhibitor is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells and regulates odontoblast differentiation and dentin formation during odontogenesis.

The SERPINE1 gene is highly involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR). The encoded protein may play a central role in tissue remodeling in chronic rhinosinusitis without nasal polyps. The 4G allele of the SERPINE1 gene has also been found to be associated with the risk of upper respiratory tract diseases (Chen TY et al. 2021).

Diseases associated with SERPINE1 include:

plasminogen activator inhibitor 1 deficiency

and

congenital plasminogen activator inhibitor type 1 deficiency.

1. Chen TY et al. (2021) Research Progress on the SERPINE1 Protein and Chronic Inflammatory Diseases of the Upper Respiratory Tract: A Literature Review. Int Arch Allergy Immunol 182:1097-1102.
2. Providence KM et al. (2008) SERPINE1 (PAI-1) is deposited into keratinocyte migration "trails" and required for optimal monolayer wound repair. Arch Dermatol Res 300:303-310.
3. Simone TM et al. (2014) SERPINE1: A Molecular Switch in the Proliferation-Migration Dichotomy in Wound-"Activated" Keratinocytes. Adv Wound Care (New Rochelle) 3:281-290.
4. Szabo R et al. (2005) Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity. Biochem J 390:231-242.