Cathepsin V: Molecular characteristics and significance in health and disease

Lecaille, Fabien; Chazeirat, Thibault; Saidi, Ahlame; Lalmanach, Gilles

doi:10.1016/j.mam.2022.101086

Cited by 18 publications

(10 citation statements)

References 178 publications

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“…Cathepsin L (CTSL) is a major member of the lysosomal cysteine protease family and belongs to the papain family. Participated in the release of antigenic peptides and maturation of MHCII class molecules, as well as in the turnover of elastin brils, intracellular antigen presentation, T cell sorting, cell apoptosis, embryonic development, and extracellular substrate lysis 41 .The expression of cathepsin L is mainly related to chondrocyte hypertrophy 42 .Research on some mammals has found that CTSL is involved in the processing of various proteins and hormonal precursors, as well as the maturation process of functional proteins. Some studies have shown that cathepsins have a damaging effect on articular cartilage in osteoarthritis and rheumatoid arthritis [43][44][45][46] .…”

Section: Discussionmentioning

confidence: 99%

A Mendelian randomization study: Association of Cathepsin with Osteoarticular Muscle Diseases

Yang,

Han,

Cui

et al. 2024

Preprint

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Objective: The cathepsin present in lysosomal cells may be closely related to bone, muscle & joint diseases (BMJD)including osteoporosis and osteoarthritis, but its specific mechanism of action still needs further research and exploration. The aim of this study is to use a two-sample Mendelian randomization (MR) comprehensive analysis to explore the causal relationship between cathepsin and the risk of BMJD. Method: Based on the published genetic data, this study used a two-sample Mendelian randomization (MR) comprehensive analysis method to explore the causality of morbidity risk between 9 cathepsins with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, peripheral arthritis(Crohn's disease, ulcerative colitis, and postdysentery joint disease), psoriatic joint disease, lower back pain, spinal stenosis, osteoporosis, bone necrosis, and connective tissue disease, cartilage diseases, benign tumors, myositis, synovitis and tenosynovitis (radial styloid tenosynovitis), shoulder periarthritis, neuromuscular junction diseases, and muscle atrophy. Meanwhile, in order to further reveal the possibility of reverse causality, we conducted a reverse Mendelian randomization analysis,using Cochran's Q test and MR Egger intercept test to evaluate the heterogeneity, horizontal pleiotropy,and stability of SNPs. Result: The study found that cathepsin B may be negatively correlated with ulcerative colitis arthritis, cathepsin E may be positively correlated with osteoarthritis, cathepsin E may be negatively correlated with musculoskeletal connective tissue diseases, cathepsin G may be positively correlated with ankylosing spondylitis, and cathepsin L2 may be positively correlated with cartilage diseases, Cathepsin S may be positively correlated with rheumatoid arthritis; through reverse MR analysis, we found that osteoporosis may lead to an increase in cathepsin B. In addition, we did not find any relationship between synovitis, tenosynovitis, shoulder periarthritis, bone necrosis, neuritis, osteoporosis,Crohn's arthritis,dysentery arthritis, psoriatic arthritis, low back pain,and cathepsin. Conclusion: Based on large-scale population studies of GWAS data, we conducted MR analysis and demonstrated a close relationship between cathepsins and BMJD from a genetic perspective, which may provide a basis for the pathogenesis of BMJD and provide new directions for future treatment strategies.

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Section: Discussionmentioning

confidence: 99%

A Mendelian randomization study: Association of Cathepsin with Osteoarticular Muscle Diseases

Yang,

Han,

Cui

et al. 2024

Preprint

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“…Cathepsin L2, also known as cathepsin V, is a human lysosomal cysteine peptidase that plays specific roles in pathological mechanisms and is crucial in the breakdown of the extracellular matrix ( 47 ). Cathepsin L2 is involved in the release of antigenic peptides, the maturation of major histocompatibility complex (MHC) class II molecules, the turnover of elastinogen fibers, as well as the cleavage of intracellular and extracellular substrates ( 48 ). It has been discovered that cathepsin L2, which is widely expressed in human tumors, plays an essential part in promoting the proliferation of bladder cancer by increasing NF-κB activity ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

The causal relationship between cathepsins and digestive system tumors: a Mendelian randomization study

Huang,

Deng,

Zhang

et al. 2024

Front. Oncol.

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

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“…Its role in melanoma progression remains unclear, but in gastric adenocarcinoma, it is involved in the migration and invasion of cancer cells [ 54 ]. Another protein identified in the CAKs medium was cathepsin V – endopeptidase, which elevated expression correlates with several types of cancer, such as colorectal and breast cancer [ 55 ]. In keratinocytes, cathepsin V plays a role in melanosome degradation [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Melanoma stimulates the proteolytic activity of HaCaT keratinocytes

et al. 2022

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

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Cathepsin V: Molecular characteristics and significance in health and disease

Cited by 18 publications

References 178 publications

A Mendelian randomization study: Association of Cathepsin with Osteoarticular Muscle Diseases

A Mendelian randomization study: Association of Cathepsin with Osteoarticular Muscle Diseases

The causal relationship between cathepsins and digestive system tumors: a Mendelian randomization study

Melanoma stimulates the proteolytic activity of HaCaT keratinocytes

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