Pathogenic Mechanisms of Collagen TypeⅦA1 (COL7A1) and Transporter Protein Transport and Golgi Organization 1 (TANGO1) in Rheumatoid Arthritis: A New Therapeutic Target
Rheumatoid arthritis (RA) is an autoimmune disorder causing chronic inflammation primarily due to collagen regulation and transport imbalances. Collagen VII A1(COL7A1), a major component of anchoring fibrils, regulates inflammation via interacting with its transporter protein Transport and Golgi org...
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2024-11-01
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| author | Debolina Chakraborty Prachi Agnihotri Lovely Joshi Mohd Saquib Swati Malik Uma Kumar Sagarika Biswas |
| author_facet | Debolina Chakraborty Prachi Agnihotri Lovely Joshi Mohd Saquib Swati Malik Uma Kumar Sagarika Biswas |
| author_sort | Debolina Chakraborty |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is an autoimmune disorder causing chronic inflammation primarily due to collagen regulation and transport imbalances. Collagen VII A1(COL7A1), a major component of anchoring fibrils, regulates inflammation via interacting with its transporter protein Transport and Golgi organization 2 homologs (TANGO1). The study revealed a significant increase in COL7A1 levels in both the plasma and PBMCs of RA patients. Additionally, a positive correlation between COL7A1 and ACCPA (anti-cyclic citrullinated peptide antibody) levels was observed among RA patients. TANGO1 mRNA expression was also found to be elevated in PBMCs. The knockdown of COL7A1 in RA synoviocytes using siRNA affected the expression of TANGO1 and inflammatory genes. Western blot analysis showed that COL7A1 si-RNA in TNF-α-induced SW982 cells reduced the expression of COL7A1, TANGO1, and NF-kBp65. The mRNA expression of inflammatory genes TNF-α, NF-kB p65, and IL-6 simultaneously decreased after the knockdown of COL7A1, as measured by qRT-PCR. An in silico analysis found 20 common interacting proteins of COL7A1 and TANGO1, with pathway enrichment analysis linking them to antigen presentation, class I and II MHC, and adaptive immunity pathways in RA. Among the common proteins, The DisGeNET database depicted that COL1A1, MIA3, SERPINH1, and GORASP1 are directly linked to RA. The molecular docking analysis of COL7A1 and TANGO1 revealed strong interaction with a −1013.4 energy-weighted score. Common RA-used drugs such as Adalimumab, Golimumab, and Infliximab were found to inhibit the interaction between COL7A1 and TANGO1, which can further impede the transport of COL7A1 from ER exit sites, indicating COL7A1 and TANGO1 as potential therapeutic targets to diminish RA progression. |
| format | Article |
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| institution | DOAJ |
| issn | 2673-5601 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Immuno |
| spelling | doaj-art-664f2f9a4b6b427ca1969ce0a1868a2d2025-08-20T02:55:45ZengMDPI AGImmuno2673-56012024-11-014446147810.3390/immuno4040029Pathogenic Mechanisms of Collagen TypeⅦA1 (COL7A1) and Transporter Protein Transport and Golgi Organization 1 (TANGO1) in Rheumatoid Arthritis: A New Therapeutic TargetDebolina Chakraborty0Prachi Agnihotri1Lovely Joshi2Mohd Saquib3Swati Malik4Uma Kumar5Sagarika Biswas6Department of Integrative & Functional Biology, Council of Scientific & Industrial Research–Institute of Genomics and Integrative Biology (CSIR–IGIB), Delhi University Campus, Mall Road, Delhi 110007, IndiaDepartment of Integrative & Functional Biology, Council of Scientific & Industrial Research–Institute of Genomics and Integrative Biology (CSIR–IGIB), Delhi University Campus, Mall Road, Delhi 110007, IndiaDepartment of Integrative & Functional Biology, Council of Scientific & Industrial Research–Institute of Genomics and Integrative Biology (CSIR–IGIB), Delhi University Campus, Mall Road, Delhi 110007, IndiaDepartment of Integrative & Functional Biology, Council of Scientific & Industrial Research–Institute of Genomics and Integrative Biology (CSIR–IGIB), Delhi University Campus, Mall Road, Delhi 110007, IndiaDepartment of Integrative & Functional Biology, Council of Scientific & Industrial Research–Institute of Genomics and Integrative Biology (CSIR–IGIB), Delhi University Campus, Mall Road, Delhi 110007, IndiaAll India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, IndiaDepartment of Integrative & Functional Biology, Council of Scientific & Industrial Research–Institute of Genomics and Integrative Biology (CSIR–IGIB), Delhi University Campus, Mall Road, Delhi 110007, IndiaRheumatoid arthritis (RA) is an autoimmune disorder causing chronic inflammation primarily due to collagen regulation and transport imbalances. Collagen VII A1(COL7A1), a major component of anchoring fibrils, regulates inflammation via interacting with its transporter protein Transport and Golgi organization 2 homologs (TANGO1). The study revealed a significant increase in COL7A1 levels in both the plasma and PBMCs of RA patients. Additionally, a positive correlation between COL7A1 and ACCPA (anti-cyclic citrullinated peptide antibody) levels was observed among RA patients. TANGO1 mRNA expression was also found to be elevated in PBMCs. The knockdown of COL7A1 in RA synoviocytes using siRNA affected the expression of TANGO1 and inflammatory genes. Western blot analysis showed that COL7A1 si-RNA in TNF-α-induced SW982 cells reduced the expression of COL7A1, TANGO1, and NF-kBp65. The mRNA expression of inflammatory genes TNF-α, NF-kB p65, and IL-6 simultaneously decreased after the knockdown of COL7A1, as measured by qRT-PCR. An in silico analysis found 20 common interacting proteins of COL7A1 and TANGO1, with pathway enrichment analysis linking them to antigen presentation, class I and II MHC, and adaptive immunity pathways in RA. Among the common proteins, The DisGeNET database depicted that COL1A1, MIA3, SERPINH1, and GORASP1 are directly linked to RA. The molecular docking analysis of COL7A1 and TANGO1 revealed strong interaction with a −1013.4 energy-weighted score. Common RA-used drugs such as Adalimumab, Golimumab, and Infliximab were found to inhibit the interaction between COL7A1 and TANGO1, which can further impede the transport of COL7A1 from ER exit sites, indicating COL7A1 and TANGO1 as potential therapeutic targets to diminish RA progression.https://www.mdpi.com/2673-5601/4/4/29rheumatoid arthritisCOL7A1TANGO1therapeutic drugsinflammation |
| spellingShingle | Debolina Chakraborty Prachi Agnihotri Lovely Joshi Mohd Saquib Swati Malik Uma Kumar Sagarika Biswas Pathogenic Mechanisms of Collagen TypeⅦA1 (COL7A1) and Transporter Protein Transport and Golgi Organization 1 (TANGO1) in Rheumatoid Arthritis: A New Therapeutic Target Immuno rheumatoid arthritis COL7A1 TANGO1 therapeutic drugs inflammation |
| title | Pathogenic Mechanisms of Collagen TypeⅦA1 (COL7A1) and Transporter Protein Transport and Golgi Organization 1 (TANGO1) in Rheumatoid Arthritis: A New Therapeutic Target |
| title_full | Pathogenic Mechanisms of Collagen TypeⅦA1 (COL7A1) and Transporter Protein Transport and Golgi Organization 1 (TANGO1) in Rheumatoid Arthritis: A New Therapeutic Target |
| title_fullStr | Pathogenic Mechanisms of Collagen TypeⅦA1 (COL7A1) and Transporter Protein Transport and Golgi Organization 1 (TANGO1) in Rheumatoid Arthritis: A New Therapeutic Target |
| title_full_unstemmed | Pathogenic Mechanisms of Collagen TypeⅦA1 (COL7A1) and Transporter Protein Transport and Golgi Organization 1 (TANGO1) in Rheumatoid Arthritis: A New Therapeutic Target |
| title_short | Pathogenic Mechanisms of Collagen TypeⅦA1 (COL7A1) and Transporter Protein Transport and Golgi Organization 1 (TANGO1) in Rheumatoid Arthritis: A New Therapeutic Target |
| title_sort | pathogenic mechanisms of collagen typeviia1 col7a1 and transporter protein transport and golgi organization 1 tango1 in rheumatoid arthritis a new therapeutic target |
| topic | rheumatoid arthritis COL7A1 TANGO1 therapeutic drugs inflammation |
| url | https://www.mdpi.com/2673-5601/4/4/29 |
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