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

Cysteine Cathepsins: From Diagnosis to Targeted Therapy of Cancer DOI Creative Commons
Ana Ercegovič Rot,

Matija Hrovatin,

Bor Bokalj

et al.

Biochimie, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

3
Non-Canonical, Extralysosomal Activities of Lysosomal Peptidases in Physiological and Pathological Conditions: New Clinical Opportunities for Cancer Therapy DOI Creative Commons

Ryan Conesa-Bakkali,

Macarena Morillo‐Huesca, Jonathan Martínez‐Fábregas

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 68 - 68

Published: Jan. 7, 2025

Lysosomes are subcellular compartments characterised by an acidic pH, containing ample variety of acid hydrolases involved in the recycling biopolymers. Among these hydrolases, lysosomal proteases have merely been considered as end-destination responsible for digestion waste proteins, trafficked to compartment through autophagy and endocytosis. However, recent reports started unravel specific roles regulation initially unexpected biological processes, both under physiological pathological conditions. Furthermore, some no longer restricted compartment, more novel non-canonical, extralysosomal targets being identified. Currently, accepted play key functions extracellular milieu, attached plasma membrane even cytosolic nuclear cell. Under conditions, proteases, activities, linked cell differentiation, gene expression, division. cancer, mostly their activities cytosol nuclei cells. In this review, we aim provide a comprehensive summary our current knowledge about extralysosomal, non-canonical with particular interest that could potentially offer new opportunities clinical intervention.

Language: Английский

Citations

0
Cathepsins in oral diseases: mechanisms and therapeutic implications DOI Creative Commons
Hao Jiang, Zuoxiang Dong, Xiaomin Xia

et al.

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

Published: June 2, 2023

Cathepsins are a type of lysosomal globulin hydrolase and crucial for many physiological processes, including the resorption bone matrix, innate immunity, apoptosis, proliferation, metastasis, autophagy, angiogenesis. Findings regarding their functions in human processes disorders have drawn extensive attention. In this review, we will focus on relationship between cathepsins oral diseases. We highlight structural functional properties related to diseases, as well regulatory mechanisms tissue cells therapeutic uses. Elucidating associated mechanism diseases is thought be promising strategy treatment may starting point further studies at molecular level.

Language: Английский

Citations

8
Adipokines regulate mesenchymal stem cell osteogenic differentiation DOI Creative Commons
Zhonghua Xu, Chenwei Xiong,

Kaisong Miao

et al.

World Journal of Stem Cells, Journal Year: 2023, Volume and Issue: 15(6), P. 502 - 513

Published: June 26, 2023

Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone engineering studies. Moreover, the conditions methods inducing are continuously advancing. Recently, with gradual recognition adipokines, research on their involvement different pathophysiological processes body is also deepening lipid metabolism, inflammation, immune regulation, energy disorders, homeostasis. At same time, role adipokines gradually described more completely. Therefore, this paper reviewed evidence MSCs, emphasizing formation regeneration.

Language: Английский

Citations

8
The Interplay of Glycosaminoglycans and Cysteine Cathepsins in Mucopolysaccharidosis DOI Creative Commons
Alexis David, Thibault Chazeirat, Ahlame Saidi

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(3), P. 810 - 810

Published: March 7, 2023

Mucopolysaccharidosis (MPS) consists of a group inherited lysosomal storage disorders that are caused by defect certain enzymes participate in the metabolism glycosaminoglycans (GAGs). The abnormal accumulation GAGs leads to progressive dysfunctions various tissues and organs during childhood, contributing premature death. As current therapies limited inefficient, exploring molecular mechanisms pathology is thus required address unmet needs MPS patients improve their quality life. Lysosomal cysteine cathepsins family proteases play key roles numerous physiological processes. Dysregulation expression activity can be frequently observed many human diseases, including MPS. This review summarizes basic knowledge on management focuses MPS, as well interplay, which may lead development MPS-associated disorders.

Language: Английский

Citations

7
Relationship between cathepsins and cardiovascular diseases: a Mendelian randomized study DOI Creative Commons
Qiaoqiao Li, Zhongzheng Zhou,

Teng Xu

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 4, 2024

Background: Cardiovascular diseases (CVDs) are the leading age-related disorders worldwide, with their prevalence increasing annually. Cathepsins protein-degrading enzymes essential for processes such as intracellular protein breakdown, apoptosis, and immune responses. Recent studies suggest a potential link between cathepsins CVDs, yet exact causal relationship remains to be elucidated. To address this, we propose using Mendelian randomization (MR) explore relationships CVDs. Methods: We obtained single nucleotide polymorphism (SNP) data from INTERVAL study, publicly accessible genome-wide association study (GWAS) dataset. Outcome SNP were sourced seven distinct GWAS datasets, ensuring comprehensive analysis across multiple cardiovascular outcomes. For MR analysis, primarily employed inverse variance weighted (IVW) method, known its efficiency when all SNPs valid instruments. This was supplemented by median MR-Egger methods provide robustness against violations of assumptions, pleiotropy. The IVW method offers precision efficiency, adds invalid instruments, helps identify correct pleiotropic biases. Cochran’s Q test utilized assess heterogeneity, sensitivity analyses conducted MR-PRESSO leave-one-out approach. Results: strength associations exposure outcome measured odds ratios (ORs), results presented 95% confidence intervals (CIs). cathepsin E increases risk myocardial infarction (MI) (OR = 1.053%, CI: 1.007–1.101, p 0.024) ischemic stroke (IS) 1.06%, 1.019–1.103, 0.004). Conversely, L2 decreases chronic heart failure (CHF) 0.922%, 0.859–0.99, 0.025) atrial fibrillation (AF) 0.956%, 0.918–0.996, 0.033). Cathepsin O associated an increased IS 1.054%, 1.008–1.102, 0.021) AF 1.058%, 1.02–1.098, 0.002). Conclusion: Our reveals that is factor MI IS, protective effects CHF AF, AF.

Language: Английский

Citations

2
Melanoma stimulates the proteolytic activity of HaCaT keratinocytes DOI Creative Commons

Justyna Mazurkiewicz,

Aleksandra Simiczyjew, Ewelina Dratkiewicz

et al.

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: Sept. 19, 2022

Abstract Background Keratinocytes constitute a major part of the melanoma microenvironment, considering their protective role towards melanocytes in physiological conditions. However, interactions with tumor cells following melanomagenesis are still unclear. Methods We used two vitro models (melanoma-conditioned media and indirect co-culture keratinocytes on Transwell inserts) to activate immortalized cancer-associated ones. Western Blotting qPCR were evaluate keratinocyte markers mediators cell invasiveness protein mRNA expression level respectively. The levels activity proteases cytokines analysed using gelatin-FITC staining, gelatin zymography, chemiluminescent enzymatic test, as well arrays. Finally, further study functional changes influenced by we assessed rate proliferation invasive abilities employing wound healing assay filter invasion method. Results HaCaT activated through incubation melanoma-conditioned medium or exhibit properties less differentiated (downregulation cytokeratin 10), which also prefer form connections cancer rather than adjacent (decreased E-cadherin). While they express only small number cytokines, variety secreted is quite prominent especially that several them never reported secretome keratinocytes’ (e.g., matrix metalloproteinase 3 (MMP3), ADAM metallopeptidase thrombospondin type 1 motif 1). Activated seem high proteolytic mediated MMP9 MMP14, reduced TIMPs (tissue inhibitor metalloproteinases), upregulation ERK increased MMP regulators-RUNX2 galectin 3. Moreover, show slightly elevated migratory abilities, however inserts. Conclusions Our offers more in-depth view residing niche, drawing attention unique factors could be support surrounding tissues.

Language: Английский

Citations

11
Cleavage of Occludin by Cigarette Smoke-Elicited Cathepsin S Increases Permeability of Lung Epithelial Cells DOI Creative Commons
Paul Bigot,

Simon Chesseron,

Ahlame Saidi

et al.

Antioxidants, Journal Year: 2022, Volume and Issue: 12(1), P. 5 - 5

Published: Dec. 21, 2022

Chronic obstructive pulmonary disease (COPD) is an irreversible mainly caused by smoking. COPD characterized emphysema and chronic bronchitis associated with enhanced epithelial permeability. Lung biopsies from smokers revealed a decreased expression level of occludin, which protein involved in the cohesion tight junctions. Moreover, occludin correlated negatively smoking history (pack-years), grades, cathepsin S (CatS) activity. Thus, we examined whether CatS could participate modulation integrity human lung barriers. Cigarette smoke extract (CSE) triggered upregulation THP-1 macrophages through mTOR/TFEB signaling pathway. In co-culture model, following exposure to CSE, permeability (16HBE NHBE) cells towards FITC-Dextran was observed, decrease level. Similar results were obtained using 16HBE NHBE cultured at air-liquid interface. The treatment siRNAs or pharmacological inhibitor restored barrier function cells, suggesting that cigarette smoke-elicited induced alteration via proteolytic injury occludin. Alongside its noteworthy resistance oxidative stress oxidants deleterious elastin-degrading potency, may also have detrimental effect on cleavage data emphasize emerging role smoking-related diseases strengthen relevance targeting COPD.

Language: Английский

Citations

9
Cathepsin V is a useful prognostic factor for colorectal cancer DOI Creative Commons
Moon-Soo Lee, Chang-Nam Kim,

Dong Wook Kang

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 262, P. 155531 - 155531

Published: Aug. 14, 2024

Molecular studies have identified various treatment-related prognostic molecules to enhance the effectiveness of colorectal cancer (CRC) treatment and improve survival rates. The expression cathepsin V in gastrointestinal cells prompted an investigation into its potential as a indicator for CRC. evaluation clinicopathological significance was conducted through immunohistochemistry tissue microarray, encompassing 142 CRC normal tissues. Overall disease-free rates, based on levels, were assessed using Kaplan-Meier method compared utilizing log-rank test. Univariate multivariate analyses, employing Cox proportional hazards model, performed identify factors. Cathepsin exhibited no correlation with age, sex, tumor location, size, or histological grade. However, it significantly correlated depth invasion, regional lymph node (LN) metastasis, distant lymphovascular involvement (all p<0.001). rates better low than high (p<0.001). analysis several factors, including grade (low vs. high), size (≤ >5 cm), (T1 ≥T2), LN tumor-node-metastasis (TNM) stage (Stage I vs ≥II), involvement, expression. Multivariate revealed that depth, are independent predictors poor survival. is frequently expressed CRC, associated prognosis. Therefore, useful marker

Language: Английский

Citations

1
Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis DOI Open Access
Gema Gómez‐Mariano, Sara Pérez-Luz, Sheila Ramos-Del Saz

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12645 - 12645

Published: Aug. 10, 2023

Acid sphingomyelinase deficiency (ASMD) or Niemann–Pick disease type A (NPA), B (NPB) and A/B (NPA/B), is a rare lysosomal storage characterized by progressive accumulation of sphingomyelin (SM) in the liver, lungs, bone marrow and, severe cases, neurons. model was established generating liver organoids from NPB patient carrying p.Arg610del variant SMPD1 gene. Liver were transcriptomic lipidomic analysis. We observed altered lipid homeostasis patient-derived showing predictable increase (SM), together with cholesterol esters (CE) triacylglycerides (TAG), reduction phosphatidylcholine (PC) cardiolipins (CL). Analysis gene expression pointed to 24 downregulated genes, including SMPD1, 26 upregulated genes that reflect stress typical disease. Altered revealed reduced enzymes could be involved hepatocytes sphyngoglycolipids glycoproteins, as well coding for different glycosidases cathepsins. Lipidic transcriptome changes support use hepatic ideal models ASMD investigation.

Language: Английский

Citations

3