SPINT2

Last update 08 May 2025

Basic Info

Synonyms

HAI-2, HAI2, Hepatocyte growth factor activator inhibitor type 2

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Introduction

Inhibitor of HGFAC (PubMed:9346890). Also inhibits plasmin, and plasma and tissue kallikrein (PubMed:9115294). Inhibits serine protease activity of TMPRSS13 (PubMed:20977675, PubMed:28710277). Inhibits serine protease activity of ST14/matriptase and PRSS8/prostasin in vitro (PubMed:28710277, PubMed:30445423).

100 Clinical Results associated with SPINT2

100 Translational Medicine associated with SPINT2

0 Patents (Medical) associated with SPINT2

321

Literatures (Medical) associated with SPINT2

01 Mar 2025·British Journal of Anaesthesia

Kappa opioid receptor internalisation-induced p38 nuclear translocation suppresses glioma progression

Article

Author: Cui, Zhibo ; Li, Yong ; She, Han ; Wang, Wenying ; Zhou, Xiaoqiong ; Cai, Ruili ; Liu, Zhengchao ; Zhang, Jun ; Shi, Yu ; Yao, Yu ; Mao, Qingxiang ; Bao, Daiqin ; Ping, Yi-Fang ; Luo, Shaliu ; Yang, Hai

BACKGROUNDRecent studies have implicated a role for perioperative medications in determining patient outcomes after surgery for malignant tumours, including relapse and metastasis.METHODSA combined approach spanned molecular, cellular, and organismal levels, including bioinformatics, immunohistochemical staining of clinical and animal samples, RNA sequencing of glioblastoma multiforme (GBM) cells with Ingenuity Pathway Analysis, lentiviral-mediated gene expression modulation, in vitro cell experiments, and in vivo orthotopic tumour transplantation.RESULTSWe observed a significant correlation between increased kappa opioid receptor (KOP receptor) expression and better prognosis in patients with glioma. Exogenous KOP receptor overexpression in GBM cells in vitro induced cell cycle arrest, suppressed cell growth, and promoted apoptosis. Conversely, reducing KOP receptor expression in GBM cells reduced the proportion of cells in S and G2/M phases, accelerating cell growth. KOP receptor overexpression inhibited glioma cell growth and prolonged survival in mice in vivo, while KOP receptor knockdown had the opposite effect. Mechanistically, internalised KOP receptors were found to bind cytoplasmic p38, facilitating its nuclear translocation and phosphorylation, which influences downstream gene expression. The selective KOP receptor agonist TRK-820 triggered KOP receptor internalisation, activated the p38 pathway, and diminished glioma cell viability in vitro.CONCLUSIONSThis combined molecular, cellular, and in vivo approach supports use of KOP receptor agonists as potential adjuvant therapeutics for glioma.

01 Feb 2025·Plant Physiology and Biochemistry

How abscisic acid collaborates in Brassica napus responses to salt and drought stress: An in silico approach

Article

Author: Lohrasebi, Tahmineh ; Dousti, Mohadese ; Minuchehr, Zarrin ; Sanjarian, Foroogh ; Mazhary, Leila ; Razavi, Khadijeh

Canola (Brassica napus sp.), the most important oily seed product in the world, is affected largely by salinity and drought stresses due to its ability to be planted in arid and semiarid regions. Therefore, studying potent genes involved in salt/drought stress response in canola would help improve abiotic stress tolerance. In this study, genes involved in response to salt and drought stresses in B. napus were investigated via sequence-read archive databases at different time points. The results were analyzed by the GALAXY server to detect DEGs. DEGs associated with short-, medium- and long-term salinity and drought stress were identified via extensive meta-analysis and robust rank aggregation methods. Subsequently, Gene Ontology (GO) analysis of the identified robust DEGs was performed via BLAST2GO. By constructing a protein-protein interaction (PPI) network with Cytoscape software, the hub genes associated with each line of salt and drought stress response were identified. Among all DEGs, HAI2 and DREB1B, which are hub genes, were selected for validation by qRT‒PCR in salt/drought-tolerant and salt/drought-sensitive cultivars of canola, Okapi and RGS, respectively, under salt and drought treatments. Fine-tuning affected the manner and time of contribution of each Abscisic Acid (ABA)-dependent and ABA-independent signaling pathway in response to salinity and drought tolerant and sensitive canola cultivars. Furthermore, the identification of hub genes through meta-analysis provided insight into the molecular responses of canola to salinity/drought stresses and the engineering of abiotic stress tolerance in canola for industrial cultivation of canola in poor-quality lands.

01 Feb 2025·Molecular & Cellular Proteomics

Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides

Article

Author: Monteiro, Wayne Denis ; Morgenlander, William ; Gray, Jeffrey J ; Larman, H Benjamin ; Miao, Yang ; Zhu, Heng ; Chu, Lee-Shin ; Dong, Xinzhong ; Jayaraman, Sahana ; Steinegger, Martin ; Jang, Sung-Eun ; Chien, Daphne Chun-Che ; Liu, Zixing ; Schütze, Konstantin ; Limjunyawong, Nathachit ; Hsiao, Meng-Hsuan

Animal venoms, distinguished by their unique structural features and potent bioactivities, represent a vast and relatively untapped reservoir of therapeutic molecules. However, limitations associated with comprehensively constructing and expressing highly complex venom and venom-like molecule libraries have precluded their therapeutic evaluation via high-throughput screening. Here, we developed an innovative computational approach to design a highly diverse library of animal venoms and "metavenoms". We used programmable M13 hyperphage display to preserve critical disulfide-bonded structures for highly parallelized single-round biopanning with quantitation via high-throughput DNA sequencing. Our approach led to the discovery of Kunitz-type domain containing proteins that target the human itch receptor Mas-related G-protein coupled receptor member X4, which plays a crucial role in itch perception. Deep learning-based structural homology mining identified two endogenous human homologs, tissue factor pathway inhibitor (TFPI), and serine peptidase inhibitor, Kunitz type 2 (SPINT2), which exhibit agonist-dependent potentiation of Mas-related G-protein coupled receptor member X4. Highly multiplexed screening of animal venoms and metavenoms is therefore a promising approach to uncover new drug candidates.

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SPINT2

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