SERPINE1

Fig1. Schematic overview of the regulatory role of plasminogen activator inhibitor-1 (PAI-1) in the plasminogen activator/plasmin system. (Machteld Sillen, 2021)

What is SERPINE1 protein?

SERPINE1 (serpin family E member 1) gene is a protein coding gene which situated on the long arm of chromosome 7 at locus 7q22. This gene encodes a member of the serine proteinase inhibitor (serpin) superfamily. This member is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), and hence is an inhibitor of fibrinolysis. The SERPINE1 protein also known as PAI1, is consisted of 402 amino acids and its molecular mass is approximately 45.1 kDa.

What is the function of SERPINE1 protein?

The primary function of SERPINE1 is to act by inhibiting specific proteases, balancing the coagulation and fibrinolytic systems by inhibiting fibrinolytic systems. SERPINE1 regulates fibrinolytic processes by preventing the activation of tissue-type plasminogen. This protein plays a key role in maintaining the balance between blood clotting and fibrinolysis. In addition, it can affect the remodeling of extracellular matrix by inhibiting the activity of plasminase, thus affecting cell behavior, and can also regulate the production and release of inflammatory mediators.

SERPINE1 Related Signaling Pathway

SERPINE1 is mainly involved in the regulation of fibrinolysis system, in addition, SERPINE1 is also involved in the regulation of thrombosis, cell migration, cell proliferation and other physiological processes. Possible signaling pathways include: SERPINE1 is a downstream target gene of TGF-β signaling pathway, and TGF-β can stimulate SERPINE1 expression. SERPINE1 expression may also be regulated by the NF-κB signaling pathway. Studies have shown that the PI3K/Akt signaling pathway may be associated with SERPINE1 expression in some environments.

SERPINE1 Related Diseases

Defects in this gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the gene product are associated with thrombophilia. Also, SERPINE1 plays a role in the process of fibrosis, which may regulate the occurrence and development of fibrosis by influencing the remodeling of extracellular matrix and TGF-β signaling pathway, such as kidney fibrosis and pulmonary fibrosis. It also plays a role in inflammation regulation, immune response, and cancer development.

Fig2. Schematic depicts the critical role of TGFβ1/Serpin E1 in promoting diabetes-accelerated kidney aging and injury via driving renal tubular premature senescence and degeneration. (Bo Han Chen, 2023)

Bioapplications of SERPINE1

In terms of biological applications, SERPINE1 as a molecular chaperone and stress protein has the potential to be used to develop new therapeutic approaches, especially in the field of cancer therapy. SERPINE1 also has some existing applications in medical research and diagnosis, such as as a biomarker for thrombotic diseases.

Case study 1: Bo Han Chen, 2023

As a leading cause of chronic kidney disease, diabetic kidney disease (DKD) involves insidious but progressive impairments of renal tubules, and is associated with premature renal aging. The underlying pathomechanisms remain elusive.

Post hoc analyses of the publicly-available renal transcriptome revealed that TGFβ1 is overexpressed in renal tubulointerstitia in patients with DKD and positively correlated with kidney aging signaling. In vitro in renal tubular epithelial cells, exposure to a diabetic milieu, stimulated with high ambient glucose and TGFβ1, elicited premature senescence, as evidenced by staining for senescence-associated β-galactosidase activity and increased expression of p16INK4A, and p53. This coincided with Serpin E1 induction. Reminiscent of the action of typical senolytics, a small molecule inhibitor of Serpin E1 substantially mitigated the pro-senescent and degenerating effects of the diabetic milieu. Moreover, inhibition of Serpin E1 abolished the diabetic insult-triggered paracrine senescence of renal tubular cells. In consistency, in patients with DKD, renal tubular expression of Serpin E1 was upregulated and positively correlated with tubular senescence and fibrosis in renal tubulointerstitia.

Fig1. Inhibition of Serpin E1 mitigated tubular cell senescence elicited by TGFβ1 in diabetic milieu. Cell lysates were processed for immunoblot analysis for fibronectin (FN).

Fig2. Increased expression of Serpin E1 is evident in renal tubules in diabetic kidney disease.

Case study 2: Wen-Fei Wei, 2023

Endothelial-mesenchymal transition (EndoMT) is an emerging adaptive process that modulates lymphatic endothelial function to drive aberrant lymphatic vascularization in the tumour microenvironment (TME); however, the molecular determinants that govern the functional role of EndoMT remain unclear. Here, the researchers show that cancer-associated fibroblast (CAF)-derived PAI-1 promoted the EndoMT of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC).

The phenotype of EndoMT in lymphatic endothelial cells (LECs), gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA or western blotting. Furthermore, association between PAI-1 expression and EndoMT in CSCC was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) databases was used to assess the association of PAI-1 with survival rate in CSCC. All the data indicate that CAF-derived PAI-1 acts as an important neolymphangiogenesis-initiating molecular during CSCC progression through modulating the EndoMT of LECs, resulting in promotion of metastasis ability in primary site. PAI-1 could serve as an effective prognostic biomarker and therapeutic target for CSCC metastasis.

Fig3. The expression of the four significant cytokines was analysed by qRT-PCR.

Fig4. Western blotting analysis of the signalling pathways activated in PAI-1-treated HDLECs.

SERPINE1 has several biochemical functions, for example, protease binding,protein binding,receptor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SERPINE1 itself. We selected most functions SERPINE1 had, and list some proteins which have the same functions with SERPINE1. You can find most of the proteins on our site.

SERPINE1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SERPINE1 here. Most of them are supplied by our site. Hope this information will be useful for your research of SERPINE1.

SGTA;SGTB;UBQLN1;UBQLN1;ORM1;PLAU;PLAT;VTN;UBQLN4