Transthyretin and Receptor for Advanced Glycation End Product’s Differential Levels Associated with the Pathogenesis of Rheumatoid Arthritis

Monu,1,2 Prachi Agnihotri,1 Mohd Saquib,1,2 Ashish Sarkar,1,2 Debolina Chakraborty,1,2 Uma Kumar,3 Sagarika Biswas1 1Council of Scientific and Industrial Research -Institute of Genomics & Integrative Biology (CSIR–IGIB), Delhi, 110007, India; 2Academy of Scientific and Innovative Research (AcSIR...

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Autores principales: Monu, Agnihotri P, Saquib M, Sarkar A, Chakraborty D, Kumar U, Biswas S
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:93dcb46c30934decab06f175b744cf662021-12-02T19:22:33ZTransthyretin and Receptor for Advanced Glycation End Product’s Differential Levels Associated with the Pathogenesis of Rheumatoid Arthritis1178-7031https://doaj.org/article/93dcb46c30934decab06f175b744cf662021-10-01T00:00:00Zhttps://www.dovepress.com/transthyretin-and-receptor-for-advanced-glycation-end-products-differe-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Monu,1,2 Prachi Agnihotri,1 Mohd Saquib,1,2 Ashish Sarkar,1,2 Debolina Chakraborty,1,2 Uma Kumar,3 Sagarika Biswas1 1Council of Scientific and Industrial Research -Institute of Genomics & Integrative Biology (CSIR–IGIB), Delhi, 110007, India; 2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; 3All India Institute of Medical Sciences, New Delhi, 110029, IndiaCorrespondence: Sagarika BiswasIntegrative and Functional Biology Department CSIR- Institute of Genomics & Integrative Biology, Mall Road, Delhi, 110 007, IndiaTel +91 11 27667602Fax +91-11-27667471; +9818004740Email sagarika.biswas@igib.res.inObjective: Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory joint disease. The identification of multifaceted etiological changes at the protein level in RA remains an important need. We aimed to identify differential proteins (DPs) and gene profiles to uncover inflammatory indicators and their association to RA pathogenesis.Methods: 2-DE and SWATH-MS were used to identify DPs in RA and healthy control plasma. Fluorescence phenylboronate gel electrophoresis (Flu-PAGE) with mass spectrometry was used for protein glycation in RA plasma. Disease specificity of identified DPs was confirmed by ELISA and Western blot analysis. The gene expressions of selected DPs were evaluated by qRT-PCR in PBMCs of RA, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), and osteoarthritis (OA). The functional implication of glycated protein was determined by in- silico and validated by in vitro analysis in fibroblast-like synoviocytes.Results: A total of 150 DPs (127 increased and 23 decreased) were identified by 2-DE and SWATH-MS analysis in RA plasma compared to healthy control (HC). Nine proteins were identified as glycated by Flu-PAGE LC-MS/MS. Transthyretin (TTR), serotransferrin, and apolipoprotein-A1 (Apo-A1) were found to be differential and glycated. ELISA and Western blot results revealed the disease-specific increased expression of TTR and RAGE in RA. The qRT-PCR results signify the aberrant gene expression of TTR and RAGE, found to be associated with RA when compared with SLE, SpA, and OA PBMCs. TTR-RAGE interactions were predicted by in-silico and validated by in-vitro analysis using RA-FLS. The increased levels of pro-inflammatory cytokines IL-6, IL-1β, TNF-α, and differently expressed TTR and RAGE were confirmed in fibroblast-like synoviocytes under inflammatory conditions.Conclusion: Our findings showed that the level of TTR was increased in RA plasma, along with an altered glycation rate. TTR and RAGE aberrant gene expression in PBMCs are the key events associated with RA, and TNF-α activates the NF-KB pathways and promote TTR and RAGE differential expressions that may have pathogenic/inflammatory significance.Keywords: rheumatoid arthritis, differential proteins, post-translational modifications, transthyretin, advanced glycation end products, receptor for advanced glycation end productsMonuAgnihotri PSaquib MSarkar AChakraborty DKumar UBiswas SDove Medical Pressarticlerheumatoid arthritis (ra)differential proteins (dps)post-translational modifications (ptm)transthyretin (ttr)advanced glycation end products (ages)receptors for advanced glycation end products (rage).PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 5581-5596 (2021)
institution DOAJ
collection DOAJ
language EN
topic rheumatoid arthritis (ra)
differential proteins (dps)
post-translational modifications (ptm)
transthyretin (ttr)
advanced glycation end products (ages)
receptors for advanced glycation end products (rage).
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle rheumatoid arthritis (ra)
differential proteins (dps)
post-translational modifications (ptm)
transthyretin (ttr)
advanced glycation end products (ages)
receptors for advanced glycation end products (rage).
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Monu
Agnihotri P
Saquib M
Sarkar A
Chakraborty D
Kumar U
Biswas S
Transthyretin and Receptor for Advanced Glycation End Product’s Differential Levels Associated with the Pathogenesis of Rheumatoid Arthritis
description Monu,1,2 Prachi Agnihotri,1 Mohd Saquib,1,2 Ashish Sarkar,1,2 Debolina Chakraborty,1,2 Uma Kumar,3 Sagarika Biswas1 1Council of Scientific and Industrial Research -Institute of Genomics & Integrative Biology (CSIR–IGIB), Delhi, 110007, India; 2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; 3All India Institute of Medical Sciences, New Delhi, 110029, IndiaCorrespondence: Sagarika BiswasIntegrative and Functional Biology Department CSIR- Institute of Genomics & Integrative Biology, Mall Road, Delhi, 110 007, IndiaTel +91 11 27667602Fax +91-11-27667471; +9818004740Email sagarika.biswas@igib.res.inObjective: Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory joint disease. The identification of multifaceted etiological changes at the protein level in RA remains an important need. We aimed to identify differential proteins (DPs) and gene profiles to uncover inflammatory indicators and their association to RA pathogenesis.Methods: 2-DE and SWATH-MS were used to identify DPs in RA and healthy control plasma. Fluorescence phenylboronate gel electrophoresis (Flu-PAGE) with mass spectrometry was used for protein glycation in RA plasma. Disease specificity of identified DPs was confirmed by ELISA and Western blot analysis. The gene expressions of selected DPs were evaluated by qRT-PCR in PBMCs of RA, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), and osteoarthritis (OA). The functional implication of glycated protein was determined by in- silico and validated by in vitro analysis in fibroblast-like synoviocytes.Results: A total of 150 DPs (127 increased and 23 decreased) were identified by 2-DE and SWATH-MS analysis in RA plasma compared to healthy control (HC). Nine proteins were identified as glycated by Flu-PAGE LC-MS/MS. Transthyretin (TTR), serotransferrin, and apolipoprotein-A1 (Apo-A1) were found to be differential and glycated. ELISA and Western blot results revealed the disease-specific increased expression of TTR and RAGE in RA. The qRT-PCR results signify the aberrant gene expression of TTR and RAGE, found to be associated with RA when compared with SLE, SpA, and OA PBMCs. TTR-RAGE interactions were predicted by in-silico and validated by in-vitro analysis using RA-FLS. The increased levels of pro-inflammatory cytokines IL-6, IL-1β, TNF-α, and differently expressed TTR and RAGE were confirmed in fibroblast-like synoviocytes under inflammatory conditions.Conclusion: Our findings showed that the level of TTR was increased in RA plasma, along with an altered glycation rate. TTR and RAGE aberrant gene expression in PBMCs are the key events associated with RA, and TNF-α activates the NF-KB pathways and promote TTR and RAGE differential expressions that may have pathogenic/inflammatory significance.Keywords: rheumatoid arthritis, differential proteins, post-translational modifications, transthyretin, advanced glycation end products, receptor for advanced glycation end products
format article
author Monu
Agnihotri P
Saquib M
Sarkar A
Chakraborty D
Kumar U
Biswas S
author_facet Monu
Agnihotri P
Saquib M
Sarkar A
Chakraborty D
Kumar U
Biswas S
author_sort Monu
title Transthyretin and Receptor for Advanced Glycation End Product’s Differential Levels Associated with the Pathogenesis of Rheumatoid Arthritis
title_short Transthyretin and Receptor for Advanced Glycation End Product’s Differential Levels Associated with the Pathogenesis of Rheumatoid Arthritis
title_full Transthyretin and Receptor for Advanced Glycation End Product’s Differential Levels Associated with the Pathogenesis of Rheumatoid Arthritis
title_fullStr Transthyretin and Receptor for Advanced Glycation End Product’s Differential Levels Associated with the Pathogenesis of Rheumatoid Arthritis
title_full_unstemmed Transthyretin and Receptor for Advanced Glycation End Product’s Differential Levels Associated with the Pathogenesis of Rheumatoid Arthritis
title_sort transthyretin and receptor for advanced glycation end product’s differential levels associated with the pathogenesis of rheumatoid arthritis
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/93dcb46c30934decab06f175b744cf66
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AT kumaru transthyretinandreceptorforadvancedglycationendproductrsquosdifferentiallevelsassociatedwiththepathogenesisofrheumatoidarthritis
AT biswass transthyretinandreceptorforadvancedglycationendproductrsquosdifferentiallevelsassociatedwiththepathogenesisofrheumatoidarthritis
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