Cathepsin B serves as a potential prognostic biomarker and correlates with ferroptosis in rheumatoid arthritis
Copyright © 2024 Elsevier B.V. All rights reserved..
BACKGROUND: Rheumatoid arthritis (RA) is a long-term, systemic, and progressive autoimmune disorder. It has been established that ferroptosis, a type of iron-dependent lipid peroxidation cell death, is closely associated with RA. Fibroblast-like synoviocytes (FLS) are the main drivers of RA joint destruction, and they possess a high concentration of endoplasmic reticulum structure. Therefore, targeting ferroptosis and RA-FLS may be a potential treatment for RA.
METHODS: Four machine learning algorithms were utilized to detect the essential genes linked to RA, and an XGBoost model was created based on the identified genes. SHAP values were then used to visualize the factors that affect the development and progression of RA, and to analyze the importance of individual features in predicting the outcomes. Moreover, WGCNA and PPI were employed to identify the key genes related to RA, and CIBERSORT was used to analyze the correlation between the chosen genes and immune cells. Finally, the findings were validated through in vitro cell experiments, such as CCK-8 assay, lipid peroxidation assay, iron assay, GSH assay, and Western blot.
RESULTS: Bioinformatics and machine learning were employed to identify cathepsin B (CTSB) as a potential biomarker for RA. CTSB is highly expressed in RA patients and has been found to have a positive correlation with macrophages M2, neutrophils, and T cell follicular helper cells, and a negative correlation with CD8 T cells, monocytes, Tregs, and CD4 memory T cells. To investigate the effect of CTSB on RA-FLS from RA patients, the CTSB inhibitor CA-074Me was used and it was observed to reduce the proliferation and migration of RA-FLS, as indicated by the accumulation of lipid ROS and ferrous ions, and induce ferroptosis in RA-FLS.
CONCLUSIONS: This study identified CTSB, a gene associated with ferroptosis, as a potential biomarker for diagnosing and managing RA. Moreover, CA-074Me, a CTSB inhibitor, was observed to cause ferroptosis and reduce the migratory capacity of RA-FLS.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:128 |
---|---|
Enthalten in: |
International immunopharmacology - 128(2024) vom: 15. Feb., Seite 111502 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Luo, Lianxiang [VerfasserIn] |
---|
Links: |
---|
Themen: |
CA-074Me |
---|
Anmerkungen: |
Date Completed 08.02.2024 Date Revised 15.02.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.intimp.2024.111502 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM366897853 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM366897853 | ||
003 | DE-627 | ||
005 | 20240215232010.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240114s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.intimp.2024.111502 |2 doi | |
028 | 5 | 2 | |a pubmed24n1294.xml |
035 | |a (DE-627)NLM366897853 | ||
035 | |a (NLM)38199197 | ||
035 | |a (PII)S1567-5769(24)00020-1 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Luo, Lianxiang |e verfasserin |4 aut | |
245 | 1 | 0 | |a Cathepsin B serves as a potential prognostic biomarker and correlates with ferroptosis in rheumatoid arthritis |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 08.02.2024 | ||
500 | |a Date Revised 15.02.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
520 | |a BACKGROUND: Rheumatoid arthritis (RA) is a long-term, systemic, and progressive autoimmune disorder. It has been established that ferroptosis, a type of iron-dependent lipid peroxidation cell death, is closely associated with RA. Fibroblast-like synoviocytes (FLS) are the main drivers of RA joint destruction, and they possess a high concentration of endoplasmic reticulum structure. Therefore, targeting ferroptosis and RA-FLS may be a potential treatment for RA | ||
520 | |a METHODS: Four machine learning algorithms were utilized to detect the essential genes linked to RA, and an XGBoost model was created based on the identified genes. SHAP values were then used to visualize the factors that affect the development and progression of RA, and to analyze the importance of individual features in predicting the outcomes. Moreover, WGCNA and PPI were employed to identify the key genes related to RA, and CIBERSORT was used to analyze the correlation between the chosen genes and immune cells. Finally, the findings were validated through in vitro cell experiments, such as CCK-8 assay, lipid peroxidation assay, iron assay, GSH assay, and Western blot | ||
520 | |a RESULTS: Bioinformatics and machine learning were employed to identify cathepsin B (CTSB) as a potential biomarker for RA. CTSB is highly expressed in RA patients and has been found to have a positive correlation with macrophages M2, neutrophils, and T cell follicular helper cells, and a negative correlation with CD8 T cells, monocytes, Tregs, and CD4 memory T cells. To investigate the effect of CTSB on RA-FLS from RA patients, the CTSB inhibitor CA-074Me was used and it was observed to reduce the proliferation and migration of RA-FLS, as indicated by the accumulation of lipid ROS and ferrous ions, and induce ferroptosis in RA-FLS | ||
520 | |a CONCLUSIONS: This study identified CTSB, a gene associated with ferroptosis, as a potential biomarker for diagnosing and managing RA. Moreover, CA-074Me, a CTSB inhibitor, was observed to cause ferroptosis and reduce the migratory capacity of RA-FLS | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a CA-074Me | |
650 | 4 | |a CTSB | |
650 | 4 | |a Ferroptosis | |
650 | 4 | |a Machine learning | |
650 | 4 | |a Rheumatoid arthritis | |
650 | 7 | |a Cathepsin B |2 NLM | |
650 | 7 | |a EC 3.4.22.1 |2 NLM | |
650 | 7 | |a Iron |2 NLM | |
650 | 7 | |a E1UOL152H7 |2 NLM | |
700 | 1 | |a Chen, Haiqing |e verfasserin |4 aut | |
700 | 1 | |a Xie, Kangping |e verfasserin |4 aut | |
700 | 1 | |a Xiang, Jing |e verfasserin |4 aut | |
700 | 1 | |a Chen, Jian |e verfasserin |4 aut | |
700 | 1 | |a Lin, Zhiping |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t International immunopharmacology |d 2001 |g 128(2024) vom: 15. Feb., Seite 111502 |w (DE-627)NLM112639542 |x 1878-1705 |7 nnns |
773 | 1 | 8 | |g volume:128 |g year:2024 |g day:15 |g month:02 |g pages:111502 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.intimp.2024.111502 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 128 |j 2024 |b 15 |c 02 |h 111502 |