SerpinB2, also known as plasminogen activator inhibitor type 2 (PAI-2), is widely described as an inhibitor of extracellular urokinase plasminogen activator. However, its real biological role remains somewhat elusive. It is substantially up-regulated under multiple inflammatory conditions and may be involved in processes like inflammation, autoimmune disorders, and carcinogenesis. High-throughput studies suggest its function in these areas, and its expression can be acutely upregulated by various stimuli, including aryl hydrocarbon receptor ligands [1,2].

In SerpinB2-deficient MMTV-PyMT mice, tumor progression was delayed, and CK8 + tumor cell dissemination to lymph nodes was reduced. RNA-Seq data showed enriched genes related to inflammatory responses, with upregulated M1 and downregulated M2 macrophage marker genes in tumors. In vitro, SerpinB2 knockdown decreased the sphere formation and migration of MDA-MB-231 cells and suppressed protumorigenic M2 polarization of RAW264.7 cells [3]. In SerpinB2 knockout mice subjected to kidney injury models, lack of SerpinB2 was associated with enhanced kidney damage and fibrosis, along with changes in inflammatory cell infiltration, macrophage phagocytosis, and migration. SerpinB2 knockout tubular cells had reduced CCL2 expression [4]. Mice deficient in SerpinB2 expression or with an active-site mutation showed reduced tail bleeding times, suggesting a role in hemostasis, likely through platelet-related mechanisms [5].

In conclusion, SerpinB2 plays roles in multiple biological processes. Through gene knockout mouse models, its functions in tumor development, immune response in kidney injury, and hemostasis have been revealed. These findings contribute to understanding its potential significance in diseases such as cancer and kidney disorders.

References:

1. Brauze, Damian. 2021. SERPINB2-its regulation and interplay with aryl hydrocarbon receptor. In Journal of applied genetics, 62, 99-105. doi:10.1007/s13353-020-00606-z. https://pubmed.ncbi.nlm.nih.gov/33387293/

2. Schroder, Wayne A, Major, Lee, Suhrbier, Andreas. . The role of SerpinB2 in immunity. In Critical reviews in immunology, 31, 15-30. doi:. https://pubmed.ncbi.nlm.nih.gov/21395508/

3. Piao, Yin Ji, Kim, Hoe Suk, Kim, Hyelim, Shen, Jun, Moon, Woo Kyung. 2024. SerpinB2 deficiency is associated with delayed mammary tumor development and decreased pro-tumorigenic macrophage polarization. In BMC cancer, 24, 792. doi:10.1186/s12885-024-12473-6. https://pubmed.ncbi.nlm.nih.gov/38956496/

4. Sen, Payel, Helmke, Alexandra, Liao, Chieh Ming, von Vietinghoff, Sibylle, Schmitt, Roland. 2020. SerpinB2 Regulates Immune Response in Kidney Injury and Aging. In Journal of the American Society of Nephrology : JASN, 31, 983-995. doi:10.1681/ASN.2019101085. https://pubmed.ncbi.nlm.nih.gov/32209589/

5. Schroder, Wayne A, Le, Thuy T, Gardner, Joy, Callaway, Leonie, Suhrbier, Andreas. 2018. SerpinB2 deficiency in mice reduces bleeding times via dysregulated platelet activation. In Platelets, 30, 658-663. doi:10.1080/09537104.2018.1535702. https://pubmed.ncbi.nlm.nih.gov/30388956/