Hpse-KO Mouse

Hpse, short for Heparanase, is a key enzyme involved in various biological processes. It plays a significant role in cancer, inflammation, and autoimmunity [4]. Heparanase is encoded by the HPSE gene and is associated with processes such as extracellular matrix remodeling, cell migration, and angiogenesis [1,4].

In multiple myeloma, HPSE SNPs were found to be associated with primary paraskeletal disease, indicating its role in promoting the development of this condition [3]. In abdominal aortic aneurysm, HPSE was identified as a biomarker, potentially conferring the risk of rupture in large aneurysms [2]. In hepatocellular carcinoma, the rs12503843 (T allele) of the HPSE gene was associated with an increased susceptibility to the disease [6]. In triple-negative breast cancer, HPSE was shown to be involved in cell proliferation and migration, with isoproterenol-induced upregulation of HPSE accelerating these processes through enhancing the transcriptional activity of HIF-1α [7]. Additionally, in herpes simplex virus-1 (HSV-1) infection, HPSE was found to play a role in viral release from infected cells and in promoting neuroinflammation and neurobehavioral deficits following intranasal HSV-1 infection [5,8].

In conclusion, Hpse is crucial in multiple disease-related biological processes. Studies on its SNPs and functions in different disease models, such as multiple myeloma, abdominal aortic aneurysm, hepatocellular carcinoma, triple-negative breast cancer, and HSV-1-related conditions, have provided insights into its role in disease development, progression, and as a potential biomarker. These findings may contribute to the development of new therapeutic strategies for these diseases.

References:

1. Ostrovsky, Olga, Vlodavsky, Israel, Nagler, Arnon. . Mechanism of HPSE Gene SNPs Function: From Normal Processes to Inflammation, Cancerogenesis and Tumor Progression. In Advances in experimental medicine and biology, 1221, 231-249. doi:10.1007/978-3-030-34521-1_8. https://pubmed.ncbi.nlm.nih.gov/32274712/

2. Xiong, Tao, Lv, Xiao-Shuo, Wu, Gu-Jie, Fu, Yi-Fan, Liu, Fu-Qiang. 2022. Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm. In Frontiers in immunology, 13, 907309. doi:10.3389/fimmu.2022.907309. https://pubmed.ncbi.nlm.nih.gov/35769488/

3. Ostrovsky, Olga, Beider, Katia, Magen, Hila, Vlodavsky, Israel, Nagler, Arnon. 2023. Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma. In Cells, 12, . doi:10.3390/cells12060913. https://pubmed.ncbi.nlm.nih.gov/36980254/

4. Ostrovsky, Olga, Baryakh, Polina, Morgulis, Yan, Vlodavsky, Israel, Nagler, Arnon. 2021. The HPSE Gene Insulator-A Novel Regulatory Element That Affects Heparanase Expression, Stem Cell Mobilization, and the Risk of Acute Graft versus Host Disease. In Cells, 10, . doi:10.3390/cells10102523. https://pubmed.ncbi.nlm.nih.gov/34685503/

5. Yadavalli, Tejabhiram, Sharma, Pankaj, Wu, David, Kapoor, Divya, Shukla, Deepak. 2022. CREB3 Plays an Important Role in HPSE-Facilitated HSV-1 Release in Human Corneal Epithelial Cells. In Viruses, 14, . doi:10.3390/v14061171. https://pubmed.ncbi.nlm.nih.gov/35746643/

6. Saad, Faten, Gadallah, Mahmoud, Daif, Ahmed, Bedair, Nahed, Sakr, Moustafa A. 2021. Heparanase (HPSE) gene polymorphism (rs12503843) contributes as a risk factor for hepatocellular carcinoma (HCC): a pilot study among Egyptian patients. In Journal, genetic engineering & biotechnology, 19, 3. doi:10.1186/s43141-020-00106-x. https://pubmed.ncbi.nlm.nih.gov/33411145/

7. Qiu, Jian, Shen, Zhongyi, Jiang, Guoqin, Ni, Qichao. . Isoproterenol-induced Upregulation of HPSE Accelerates Triple-negative Breast Cancer Cell Proliferation and Migration through Enhancing the Transcriptional Activity of HIF-1α. In Anti-cancer agents in medicinal chemistry, 23, 470-477. doi:10.2174/1871520622666220817125817. https://pubmed.ncbi.nlm.nih.gov/35980070/

8. Borase, Hemant, Patil, Chandrashekhar D, Valyi-Nagy, Tibor, Shukla, Deepak. 2025. HPSE-mediated proinflammatory signaling contributes to neurobehavioral deficits following intranasal HSV-1 infection. In mBio, 16, e0376524. doi:10.1128/mbio.03765-24. https://pubmed.ncbi.nlm.nih.gov/40013778/