Mendelian randomization analysis explores the causal relationship between cathepsins and osteoarthritis DOI Creative Commons
Yifeng Huang, Haoshaqiang Zhang,

Xinru Xie

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 31, 2024

Abstract Osteoarthritis, a primary etiology of joint dysfunction, entails multifaceted pathogenesis. Cathepsins, cysteine proteases localized within lysosomes, exert pivotal roles across diverse physiological and pathological contexts. Although observational inquiries suggest an interrelation between cathepsins osteoarthritis, the etiological nexus remains elusive. Employing Mendelian randomization analysis, this investigation endeavors to elucidate causal nexus. Univariate analysis reveals plausible augmentation in osteoarthritis risk concomitant with decline cathepsin S levels. Conversely, reverse posits that might precipitate reduction L2 Multivariable encompassing 9 as covariates, demonstrates potential collaborative effect elevated F levels diminished levels, thereby accentuating risk. In summation, emerges prospective biomarker for conferring implications diagnostic therapeutic paradigms targeting ailment.

Language: Английский

Cathepsin H: Molecular characteristics and clues to function and mechanism DOI
Yanfeng Wang, Juan Zhao,

Yebo Gu

et al.

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 212, P. 115585 - 115585

Published: May 5, 2023

Language: Английский

Citations

27
Cysteine Cathepsins as Therapeutic Targets in Immune Regulation and Immune Disorders DOI Creative Commons
Emanuela Senjor, Janko Kos, Milica Perišić Nanut

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 476 - 476

Published: Feb. 7, 2023

Cysteine cathepsins, as the most abundant proteases found in lysosomes, play a vital role several processes—such protein degradation, changes cell signaling, morphology, migration and proliferation, energy metabolism. In addition to their lysosomal function, they are also secreted may remain functional extracellular space. Upregulation of cathepsin expression is associated with pathological conditions including cancer, neurodegeneration, immune-system dysregulation. this review, we present an overview cysteine-cathepsin involvement possible targeting options for mitigation aberrant function immune disorders such inflammation, autoimmune diseases, response cancer.

Language: Английский

Citations

21
Compensational role between cathepsins DOI Creative Commons

Urša Pečar Fonović,

Janko Kos, Ana Mitrović

et al.

Biochimie, Journal Year: 2024, Volume and Issue: 226, P. 62 - 76

Published: April 23, 2024

Cathepsins, a family of lysosomal peptidases, play crucial role in maintaining cellular homeostasis by regulating protein turnover and degradation as well many specific regulatory actions that are important for proper cell function human health. Alterations the activity expression cathepsins have been observed diseases such cancer, inflammation, neurodegenerative disorders, bone remodelling-related conditions others. These changes not exclusively harmful, but rather appear to be compensatory response on lack one cathepsin order maintain tissue integrity. The upregulation inhibition or dysfunction other suggests fine-tuned system proteolytic balance understanding may improve therapeutic potential cathepsin's inhibitors. Selectively targeting modulating their could offer new treatment strategies number diseases. This review emphasises need comprehensive research into biology context disease. identification involved responses, elucidation underlying molecular mechanisms development targeted interventions lead innovative approaches.

Language: Английский

Citations

8
Therapeutic cysteine protease inhibitors: a patent review (2018–present) DOI

Giulia Barchielli,

Antonella Capperucci, Damiano Tanini

et al.

Expert Opinion on Therapeutic Patents, Journal Year: 2024, Volume and Issue: 34(1-2), P. 17 - 49

Published: Feb. 1, 2024

Cysteine proteases are involved in a broad range of biological functions, ranging from extracellular matrix turnover to immunity. Playing an important role the onset and progression several diseases, including cancer, immune-related neurodegenerative disease, viral parasitic infections, cysteine represent attractive drug target for development therapeutic tools.

Language: Английский

Citations

6
The causal relationship between cathepsins and digestive system tumors: a Mendelian randomization study DOI Creative Commons

Xupeng Huang,

Houbo Deng, Bo Zhang

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: March 25, 2024

Background Multiple studies have confirmed the significant role of cathepsins in development and progression digestive system tumors. However, further investigation is needed to determine causal relationships. Methods We conducted a two-sample bidirectional Mendelian randomization (MR) study using pooled data from genome-wide association (GWAS) assess associations between nine (cathepsin B, E, F, G, H, L2, O, S, Z) six types tumors, including hepatocellular carcinoma (HCC), pancreatic cancer (PCa), biliary tract (BTC), colorectal (CRC), gastric (GC), esophageal (EC). employed following methods inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran’s Q, MR-PRESSO, MR-Egger intercept test leave-one-out sensitivity analysis. The STROBE-MR checklist for reporting MR was used this study. Results risk HCC increased with high levels cathepsin G (IVW: p = 0.029, odds ratio (OR) 1.369, 95% confidence interval (CI) 1.033-1.814). Similarly, BTC associated elevated B 0.025, OR 1.693, CI 1.070-2.681). Conversely, reduction PCa H 0.027, 0.896, 0.812-0.988). Lastly, L2 were found lower CRC 0.034, 0.814, 0.674-0.985). Conclusion Our findings confirm relationship which can offer valuable insights diagnosis treatment

Language: Английский

Citations

5
Cathepsins and Skin Cancer (Malignant Melanoma, Basal Cell Carcinoma, and Squamous Cell Carcinoma): Insight From Genetic Correlation and Mendelian Randomization DOI Creative Commons
Xianglong Li, Shaofeng Yang,

Zhong Du

et al.

Clinical Cosmetic and Investigational Dermatology, Journal Year: 2025, Volume and Issue: Volume 18, P. 553 - 566

Published: March 1, 2025

Background: Multiple studies have indicated that cathepsins (Cats) play a crucial role in the development and progression of skin cancer. However, most these are observational may be influenced by external variables, necessitating further research to establish causal relationships. Methods: We conducted two-sample, two-way Mendelian randomization (MR) study utilizing pooled data from genome-wide association (GWAS) evaluate between 9 Cats (Cat-B, E, F, G, H, L2, O, S, Z) 3 types cancer, including malignant melanoma (MM), basal cell carcinoma (BCC), squamous (SCC). Our analysis employed several methods, inverse variance weighting (IVW), MR-Egger, weighted median, Cochran's Q test, MR-Egger intercept leave-one-out sensitivity analysis. Furthermore, bioinformatics loci linked cancer was performed explore potential molecular mechanisms. Results: Genetically predicted increases Cat-F Cat-O levels were found correlated with higher risk BCC, while increased Cat-L2 associated reduced incidence SCC. Bioinformatics suggested differentially expressed genes located near Cats-related could potentially influence BCC SCC modulating relevant signaling pathways tumor microenvironment. Conclusion: link By conducting bioinformatic genetic related we able gain better understanding mechanisms driving this association. This can provide valuable insights into diagnosis treatment Keywords: Cathepsins, Skin Genome-wide study, randomization, Bioinformatic

Language: Английский

Citations

0
Appraising the causal role of cathepsins in genitourinary carcinoma: a two-sample mendelian randomization and prospective study based on 36,225 individuals DOI Creative Commons

Qiyu Zhu,

Dingbang Liu,

Haoyang Liu

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 31, 2025

Cathepsin family proteases play an important role in the carcinogenesis of genitourinary carcinomas. However, causality between serum cathepsin levels and carcinomas remains uninvestigated. In this study, we conducted a two-sample Mendelian Randomization (MR) analysis exploring causal association different types cathepsins Univariate, bidirectional multivariate MR analyses were based on genome-wide studies. Moreover, linkage disequilibrium score regression (LDSC) analysis, colocalization transcriptomic also performed. 36,225 Individual data from UK biobank was utilized for further validation. Our findings revealed seven associations following univariate which five correlations validated analysis. S (CTSS) positively associated with papillary renal cell carcinoma (pRCC) [IVW: OR (95%CI) 1.444 (1.103-1.890), p: 8*10-3], LDSC indicated genetic correlation CTSS pRCC [rg (SE): 0.559 (0.225); 0.013]. Other included B (CTSB), testicular non-seminoma, L2 (CTSL2/CTSV), negatively overall kidney cancer pRCC. Transcriptomic biobank, CTSL2 found to be risk [HR 0.567 (0.368, 0.873), 0.01]. Cathepsins played urogenital carcinogenesis. Further large-scale studies are warranted extended

Language: Английский

Citations

0
Cystatin M/E, Cathepsin V and Asparaginyl Endopeptidase: New actors of the proteolytic balance in lung fibrosis DOI

B. Rigoux,

Alexandre David,

R. Allouche

et al.

Revue des Maladies Respiratoires, Journal Year: 2025, Volume and Issue: 42(4), P. 222 - 222

Published: April 1, 2025

Language: Английский

Citations

0
Cathepsin V regulates cell cycle progression and histone stability in the nucleus of breast cancer cells DOI Creative Commons
Naphannop Sereesongsaeng, James F. Burrows, Christopher J. Scott

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 6, 2023

Introduction: We previously identified that Cathepsin V (CTSV) expression is associated with poor prognosis in ER+ breast cancer, particularly within the Luminal A subtype. Examination of molecular role protease tumours, revealed CTSV promotes tumour cell invasion and proliferation, addition to degradation luminal transcription factor, GATA3, via proteasome. Methods: Cell line models expressing shRNA or transfected overexpress were used examine impact on proliferation by MTT assay flow cytometry. Western blotting analysis was identify histone chaperone protein expression. fractionation confocal microscopy illustrate presence nuclear compartment. Results: In this work we have has an cancer depleted cells exhibiting delayed progression through G2/M phase cycle. Further investigation can control levels histones H3 H4 regulating their sNASP. discovered localised compartment cells, mediated a bipartite localisation signal (NLS) sequence required for cycle stability cells. Discussion: Collectively these findings support hypothesis targeting may utility as novel therapeutic target impairing manipulating stabilisation.

Language: Английский

Citations

10
Molecular Mechanisms Underlying Vascular Remodeling in Hypertension DOI Creative Commons
Xinyi Zeng, Yan Yang

Reviews in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 25(2)

Published: Feb. 20, 2024

Hypertension, a common cardiovascular disease, is primarily characterized by vascular remodeling. Recent extensive research has led to significant progress in understanding its mechanisms. Traditionally, remodeling been described as unidirectional process which blood vessels undergo adaptive or maladaptive Adaptive involves an increase vessel diameter response increased flow, while refers the narrowing thickening of pathological conditions. However, recent revealed that much more complex. It now understood dynamic interplay between various cellular and molecular events. This different cell types, including endothelial cells, smooth muscle immune well their interactions with extracellular matrix. Through these interactions, intricate changes structure function stimuli. Moreover, factors mechanisms such renin-angiotensin-aldosterone system (RAS), oxidative stress, inflammation, matrix (ECM), sympathetic nervous (SNS) mechanical stress impact arterial wall. These may lead circulatory diseases are primary causes long-term increases systemic resistance hypertensive patients. Additionally, presence stem cells adventitia, media, intima plays crucial role disease development. In future, will focus on examining underlying contributing develop potential solutions for hypertension treatment. review provides us fresh perspective remodeling, undoubtedly sparking further efforts aimed at uncovering potent treatments enhanced preventive control measures this disease.

Language: Английский

Citations

3