在炎症性肠道疾病中检测囊类甲素的活性
Bethany M Anderson1, Alexander R Ziegler1, Rhiannon I Campden2
1Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia.
Scientific reports
|December 23, 2025
概括
卡瑟普辛S可能有助于炎症性肠病 (IBD) 症状,性结肠炎患者的水平增加. 虽然抑制甲素S在小鼠中显示出一些益处,但需要进一步的策略来有效地治疗向.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 素S是一种囊蛋白酶,与炎症性肠病 (IBD) 和内脏疼痛有关.
- 它的促炎作用表明它与其他IBD症状有关.
- 了解大肠炎中甲素激活对于治疗的发展至关重要.
研究的目的:
- 为了研究 cathepsin S 和 cathepsin X 在实验性结肠炎中的作用.
- 评估甲素S抑制对大肠炎症状的影响.
- 在人类性结肠炎和小鼠结肠炎模型中探索甲素激活.
主要方法:
- 基于活动的探针用于测量人类和小鼠结肠炎中氨酸甲素激活.
- 在性结肠炎患者的便和粘膜活检分析.
- 在cathepsin S和X缺乏的小鼠中诱导大肠炎,然后给予cathepsin S抑制剂 (LY3000328).
主要成果:
- 在性结肠炎患者中便中甲素S的增加;粘膜水平不变.
- 在小鼠结肠炎粘膜中增加了cathepsin S和X活性;光线cathepsin S显著增加.
- 在小鼠中,甲素S缺乏减少了直肠出血和腹壮大,但其他结肠炎指标保持不变. 药物抑制导致补偿性蛋白酶的上调和组织学的恶化.
结论:
- 卡塞普辛S,而不是卡塞普辛X,似乎有助于某些实验性结肠炎症状.
- 药理上抑制 cathepsin S 可能需要改进的策略来克服补偿上调.
- 卡塞普辛S是结肠炎的潜在治疗标,需要进一步研究持续抑制方法.
相关概念视频
01:30Inflammatory Bowel Disease II: Crohn's Disease
912
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
912
01:29Drugs for Treatment of Ulcerative Colitis in IBD
416
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
416
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
609
Various diagnostic tests are employed in the diagnostic process for Inflammatory Bowel Disease (IBD), particularly to differentiate between Crohn's disease and ulcerative colitis.
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
609
01:17Chronic Bowel Disorders: Introduction
722
Chronic bowel diseases are a group of long-term conditions affecting the digestive tract, characterized by inflammation and damage to the gut lining. These conditions primarily include irritable bowel syndrome and inflammatory bowel disease.
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
722
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
437
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
437
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
854
Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
854