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更新于：2025-05-07

SPINT1

更新于：2025-05-07

基本信息

别名

HAI、HAI-1、HAI1

+ [5]

简介

Inhibitor of HGFAC (PubMed:9045658). Inhibits serine protease activity of ST14/matriptase in vitro (PubMed:28710277). Inhibits serine protease activity of TMPRSS13, via the BPTI/Kunitz inhibitor 1 domain (PubMed:20977675).

关联

项与 SPINT1 相关的药物

CN117624368

专利挖掘

靶点

SPINT1

作用机制-

在研机构

Abmart Inc. [+1]

原研机构

Abmart Inc. [+1]

在研适应症

肝病 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SPINT1 相关的临床结果

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100 项与 SPINT1 相关的转化医学

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0 项与 SPINT1 相关的专利（医药）

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668

项与 SPINT1 相关的文献（医药）

2025-02-01·Pathology - Research and Practice

Loss of tumor cell surface hepatocyte growth factor activator inhibitor-1 predicts worse prognosis in esophageal squamous cell carcinoma

Article

作者: Sato, Yuichiro ; Fukushima, Tsuyoshi ; Ikenoue, Makoto ; Yamamoto, Koji ; Kataoka, Hiroaki ; Kiwaki, Takumi ; Umekita, Yoshiko ; Kawaguchi, Makiko ; Takeno, Shinsuke

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is an epithelial type-1 transmembrane protease inhibitor that regulates the pericellular activities of hepatocyte growth factor activator and type-2 transmembrane serine proteases. It is strongly expressed in the stratified squamous epithelium and functions on the cell surface. We previously reported that the cell surface immunoreactivity of HAI-1 was reduced at the invasion front of oral squamous cell carcinoma. In this study, we investigate the relationship between cell surface HAI-1 (csHAI-1) and prognosis of esophageal squamous cell carcinoma (ESCC) after surgery. The effect of HAI-1 knockdown on cultured ESCC cells was also analyzed in vitro. HAI-1 exhibited distinct cell surface immunoreactivity in normal esophageal epithelium. In contrast, alterations in HAI-1 immunoreactivity were frequent in cancer cells, which exhibited aberrant intracytoplasmic localization and decreased cell surface immunoreactivity. The preservation of csHAI-1 immunoreactivity was a sign of a well-differentiated phenotype of ESCC cells. The decreased csHAI-1 was associated with shorter overall survival (OS) and disease-free survival (DFS) in the patients. In 55 cases of early (T1) ESCC cases, decreased csHAI-1 also predicted poor OS and DFS. The loss of HAI-1 enhanced migration and invasion of ESCC cells in vitro. These results suggest that the decreased cell surface immunoreactivity of HAI-1 is associated with a less differentiated phenotype and worse prognosis in ESCC. The cell surface-localized HAI-1 may serve as a promising marker for predicting recurrence and prognosis of ESCC.

2025-01-01·Life Sciences

Intracellular autoactivation and surface location of hepsin, TMPRSS2, and TMPRSS13

Article

作者: Wang, Di ; Li, Hui ; Zhu, Rui ; Zhang, Ce ; Chen, Wenjun ; Shi, Lingyun ; Jin, Zili ; Zhang, Yue

AIMSHepsin (HPN), a Type II transmembrane serine protease (TTSP), is involved in hepatocyte metabolism and various diseases. It undergoes autoactivation on the surface of human hepatoma cells, a mechanism not observed in other cell types. This study aims to explore HPN activation and surface expression in endometrial epithelial cells.MATERIALS AND METHODSWe studied HPN zymogen activation and cell surface expression in human embryonic kidney 293 and endometrial epithelial AN3CA and Ishikawa cells using site-directed mutagenesis, Western blotting, flow cytometry, and immunostaining. Treatments with brefeldin A (BFA) and monensin, along with co-transfection assays, were employed to assess HPN activation and expression before reaching the cell surface. We also analyzed the activation and expression of TMPRSS2 and TMPRSS13 and examined the effect of the serine protease inhibitor HAI-1 on these proteases.KEY FINDINGSHPN zymogen autoactivates in the endoplasmic reticulum (ER) and Golgi apparatus. Its active form reduces cell surface expression through trans-autodegradation, a mechanism also applicable to in TMPRSS2 and TMPRSS13. Additionally, HAI-1 interacts with these TTSPs in different ways: it inhibits HPN activation and stabilizes its cell-surface expression; it inhibits TMPRSS2 activation without affecting its cell-surface expression; and it facilitates TMPRSS13 activation, protecting it from degradation and stabilizing its cell surface expression.SIGNIFICANCEThese results revealed an intracellular autoactivation and expression mechanism of HPN, TMPRSS2, and TMPRSS13, differing from the extracellular activated TTSPs. These findings provide new insights into the diverse mechanisms in regulating TTSP activation, potentially aiding in treating TTSP-related endometrial diseases.

2024-12-01·Protein Science

Kunitz‐type trypsin inhibitor from durian (Durio zibethinus) employs a distinct loop for trypsin inhibition

Article

作者: Deetanya, Peerapon ; Sabat, Grzegorz ; Pattaradilokrat, Sittiporn ; Chaisuekul, Chatchawan ; Wangkanont, Kittikhun ; Limsardsanakij, Kakanang

AbstractKunitz‐type trypsin inhibitors are ubiquitous in plants. They have been proposed to be a part of a defense mechanism against herbivores. Trypsin inhibitors also have potential applications in the biotechnology industry, such as in mammalian cell culture. We discovered that durian (Durio zibethinus) seed contains Kunitz‐type trypsin inhibitors as identified by N‐terminal sequencing and mass spectrometry. Eleven new trypsin inhibitors were cloned. The D. zibethinus trypsin inhibitors (DzTIs) that are likely expressed in the seed were produced as recombinant proteins and tested for trypsin inhibitory activity. Their inhibitory activity and crystal structures are similar to the soybean trypsin inhibitor. Surprisingly, a crystal structure of the complex between DzTI‐4, the DzTI with the lowest inhibitory constant, and bovine trypsin revealed that DzTI‐4 utilized a novel tryptophan‐containing β1‐β2 loop to bind trypsin. Site‐direct mutagenesis confirmed the inhibitory role of this loop. DzTI‐4 was not toxic to the HEK293 cells and could be used in place of the soybean trypsin inhibitor for culturing the cells under serum‐free conditions. DzTI‐4 was not toxic to mealworms. However, a mixture of DzTIs extracted from durian seed prevented weight gain in mealworms, suggesting that multiple trypsin inhibitors are required to achieve the antinutritional effect. This study highlights the biochemical diversity of the inhibitory mechanism of Kunitz‐type trypsin inhibitors and provides clues for further application of these inhibitors.

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