Ask about this productRelated genes to: SPINT2 Blocking Peptide
- Gene:
- SPINT2 NIH gene
- Name:
- serine peptidase inhibitor, Kunitz type 2
- Previous symbol:
- -
- Synonyms:
- Kop, HAI-2
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-23
- Date modifiied:
- 2016-06-24
Related products to: SPINT2 Blocking Peptide
Related articles to: SPINT2 Blocking Peptide
- All oligodendrogliomas have a characteristic 1p/19q co-deletion that alters the expression of hundreds of genes on both affected chromosomal arms. The search for genes on 1p and 19q that drive oligodendroglioma development has only made little progress over the last years. Therefore, a computational network-based approach for the analysis of single-cell oligodendroglioma transcriptomes is developed to predict potential driver gene candidates within the region of the 1p/19q co-deletion purely based on tumor cells. Nine genes with strong impact on signaling pathways (, , , , , , , , and ) and 6 partially overlapping genes with strong impact on immune pathways (, , , , , and ) were consistently predicted in at least 2 of the 3 analyzed oligodendrogliomas. Almost all of these genes are known to play important roles in growth, proliferation, and stem cells of closely related gliomas, but also roles in migration or reprogramming of the microenvironment had been reported in experimental glioma studies. Comparisons to a previous network-based bulk oligodendroglioma analysis and additional evaluations of the expression behavior of candidate genes in related normal brain cells further strengthen the study. Additional validations based on 2 independent oligodendrogliomas support the candidate genes. Robustness of the predictions is shown for imputed and nonimputed data. Strengths of the network-based approach are demonstrated by comparisons to related approaches. All findings clearly suggest that the developed network-based approach for the analysis of single-cell tumor transcriptomes is able to predict novel potential driver gene candidates for oligodendrogliomas. These are very valuable information for future experimental studies. The computational network-based approach can also be transferred to the analysis of single-cell transcriptomes of other types of cancer. - Source: PubMed
Publication date: 2026/05/04
Seifert Michael - Pericellular proteolysis is essential for maintaining tissue homeostasis. Central to this process are hepatocyte growth factor activator inhibitor-1 (HAI-1) and HAI-2, membrane-bound inhibitors that regulate type II transmembrane serine proteases, including matriptase and prostasin, through high-affinity Kunitz domains. This review summarizes current understanding of their molecular structures, physiological roles, and cancer-related clinical relevance. Genetic models reveal HAI-1 is critical for placental and skin development, while HAI-2 is crucial for neural tube closure and intestinal integrity. In cancer, HAIs generally act as tumor suppressors. Their downregulation, often via promoter hypermethylation, leads to excessive activation of hepatocyte growth factor/c-MET or protease-activated receptor-2/NF-κB signaling, promoting epithelial-mesenchymal transition and cancer progression. Clinically, reduced HAI levels in tumors correlate with metastasis and poor prognosis in several carcinomas. Paradoxically, elevated HAI expression in certain cancers suggests context-dependent pro-tumor functions. Emerging evidence links HAI loss to immune suppression, notably via M2 macrophage polarization in lung cancer. Finally, we highlight future directions for identifying tissue-specific serine proteases, downstream signaling, and therapeutic strategies, including recombinant mimetics and epigenetic reactivation, in precision oncology. In conclusion, HAI-1 and HAI-2 are key regulators of tissue homeostasis and cancer, with overlapping yet distinct functions, which present promising opportunities for therapeutic targeting. - Source: PubMed
Publication date: 2026/02/19
Chen Chun-YingLin Tai-NoHuang Hsiang-Po - Although diarrhea is common in COVID-19, its underlying mechanisms remain unclear. Using clinical data from 3023 patients and single-cell RNA sequencing of colonic tissues, we found that diarrhea was associated with higher disease severity and mortality. scRNA-seq (n = 1 COVID-19 patient with diarrhea) of colonic tissue from deceased patient, and experimental validation to elucidate the mechanisms of SARS-CoV-2-induced diarrhea and identify potential therapeutic targets. Clinical analysis revealed that diarrhea was associated with more severe disease and higher mortality rates. scRNA-seq identified significant downregulation of membrane transporters (SLC9A3, SLC26A3, and SPINT2) in colonic epithelial cells of colonic tissue from one deceased COVID-19 patient. Gene regulon network analysis pinpointed PPARA as a master regulator of these proteins, with its activity suppressed post-infection. Further experiments confirmed that E protein stimulation reduced PPARA activity and the expression of membrane transporters, leading to a diarrheal phenotype (OR = 3.33 for diarrhea as risk factor) in vitro cell culture models. Interestingly, we found PPARA activity was also decreased in SARS-CoV-2-infected lung epithelial cells, where it regulated CFTR expression, contributing to pneumonia. Treatment with PPARA agonists rescued the expression of these proteins, mitigating both diarrheal and pneumonia phenotypes. Our findings reveal a common mechanism by which the SARS-CoV-2 E protein inhibits PPARA activity in both colonic and lung epithelial cells, leading to severe clinical outcomes. PPARA agonists may represent a novel therapeutic strategy for COVID-19-associated diarrhea and pneumonia in vitro cell culture models. - Source: PubMed
Publication date: 2026/02/01
Wu QiuyueZhou MengyuanFeng XiaoyueShen YiJiang WeijunLiu XueyanLiu ZhenyuChen MinZhang JingWang FangyuSong XiaodongXu WeijunZhou HongjianXia Xinyi - Transmembrane protease serine (TMPRSS)2 is a cell surface host protease, which plays a decisive role in viral infections. This trypsin-like enzyme cleaves the spike protein of coronaviruses [e.g. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and the hemagglutinin protein of influenza viruses, enabling viral membrane fusion and subsequent viral cell entry. Consequently, TMPRSS2 is an attractive therapeutic target, and it is of utmost importance to produce wildtype, enzymatically active recombinant TMPRSS2 for drug development purposes. We present the first successful strategy for the expression of wildtype and proteolytically fully active ectodomain of human and Syrian hamster TMPRSS2 in mammalian cells. To achieve that, we co-expressed the TMPRSS2 ectodomain with its natural inhibitor, hepatocyte growth factor activator inhibitor-2, which yielded substantial amounts of secreted, native protease. Most of the recombinant TMPRSS2 was secreted as zymogen, which was activated during purification. The purified activated recombinant TMPRSS2 ectodomain cleaved synthetic and protein substrates with high efficiency (kcat/KM in the 104-106 M-1s-1 range). To study the mechanism of auto-activation, we expressed zymogen TMPRSS2 mutants as well. We found that the zymogen is an ideal substrate for the active protease as it cleaves it extremely efficiently. We also showed that zymogen TMPRSS2 itself has a weak proteolytic activity, which can initiate the auto-activation process. We demonstrated that a related cell surface protease, TMPRSS13, is also able to activate zymogen TMPRSS2. Our findings prove both a zymogen trans(auto)-activation as well as a TMPRSS13-based cross-activation mechanism, the latter supporting that type II transmembrane serine proteases can form a pericellular proteolytic cascade. - Source: PubMed
Végh BarbaraKocsis AndreaDobó JózsefBalczer JúliaKiss BencePál GáborGál Péter - Gallbladder cancer (GBC) is a highly aggressive malignancy characterized by poor prognosis and limited therapeutic options, largely due to late-stage diagnosis and a lack of defined molecular targets. This is the first study to elucidate the molecular mechanism by which SPINT2 governs GBC progression through regulation of ferroptosis, linking it to ACSL4 stability and tumor suppression. Although SPINT2 has been implicated as a tumor suppressor in multiple cancer types, its biological function and mechanistic role in GBC have remained elusive. In this study, we identify SPINT2 as a key regulator of ferroptosis in GBC. Functional assays demonstrated that SPINT2 suppresses tumor cell proliferation in vitro and tumorigenicity in vivo. Metabolomic profiling revealed that SPINT2 deficiency alters lipid metabolism and reduces susceptibility to ferroptosis. Mechanistically, SPINT2 interacts with ACSL4 and prevents its ubiquitination by the E3 ligase NEDD4L, thereby stabilizing ACSL4 protein and promoting ferroptotic cell death. Clinically, low SPINT2 expression was significantly associated with poor differentiation, advanced tumor stage, and worse overall survival. Collectively, these findings position SPINT2 as a pivotal modulator of the ferroptotic pathway in GBC and highlight its translational promise as both a prognostic biomarker and a therapeutic entry point for ferroptosis-based interventions in GBC patients. - Source: PubMed
Publication date: 2025/10/09
Ye PengYang XiaolongWang HaodongRen YifanGao MingWang YanGuo YarongSun YuqingXu Jun