Amelioration of collagen antibody induced arthritis in mice by an antibody directed against the fibronectin type III repeats of tenascin-C

Mehta, Brij Bhushan; Tiwari, Anil; Sharma, Saniya; Shukla, Ashu; Sharma, Mukut; Vasishta, Rakesh Kumar; Sen, Ramesh Kumar; Sharma, Aman; Luthra-Guptasarma, Manni

doi:10.1016/j.intimp.2018.02.022

Cited by 10 publications

(5 citation statements)

References 40 publications

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“…It amplifies Ang II-induced cardiac inflammation, promoting the production of pro-inflammatory factors such as IL-6 and macrophages, thus influencing macrophage polarization and intensifying macrophage-mediated myocardial fibrosis [ 32 33 ]. Studies have also shown that inhibiting TN-C expression can mitigate ventricular fibrosis following myocardial infarction, reduce liver fibrosis induced by hepatitis, and alleviate joint fibrosis in rheumatoid arthritis [ 33 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting myocardial inflammation: investigating the therapeutic potential of atrial natriuretic peptide in atrial fibrosis

Zhu,

Li,

Bai

et al. 2024

Mol Biol Rep

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Background Atrial Fibrillation (AF), a prevalent arrhythmic condition, is intricately associated with atrial fibrosis, a major pathological contributor. Central to the development of atrial fibrosis is myocardial inflammation. This study focuses on Atrial Natriuretic Peptide (ANP) and its role in mitigating atrial fibrosis, aiming to elucidate the specific mechanisms by which ANP exerts its effects, with an emphasis on fibroblast dynamics. Methods and results The study involved forty Sprague-Dawley rats, divided into four groups: control, Angiotensin II (Ang II), Ang II + ANP, and ANP only. The administration of 1 µg/kg/min Ang II was given to Ang II and Ang II + ANP groups, while both Ang II + ANP and ANP groups received 0.1 µg/kg/min ANP intravenously for a duration of 14 days. Cardiac fibroblasts were used for in vitro validation of the proposed mechanisms. The study observed that rats in the Ang II and Ang II + ANP groups showed an increase in blood pressure and a decrease in body weight, more pronounced in the Ang II group. Diastolic dysfunction, a characteristic of the Ang II group, was alleviated by ANP. Additionally, ANP significantly reduced Ang II-induced atrial fibrosis, myofibroblast proliferation, collagen overexpression, macrophage infiltration, and the elevated expression of Interleukin 6 (IL-6) and Tenascin-C (TN-C). Transcriptomic sequencing indicated enhanced PI3K/Akt signaling in the Ang II group. Furthermore, in vitro studies showed that ANP, along with the PI3K inhibitor LY294002, effectively reduced PI3K/Akt pathway activation and the expression of TN-C, collagen-I, and collagen-III, which were induced by Ang II. Conclusions The study demonstrates ANP’s potential in inhibiting myocardial inflammation and reducing atrial fibrosis. Notably, ANP’s effect in countering atrial fibrosis seems to be mediated through the suppression of the Ang II-induced PI3K/Akt-Tenascin-C signaling pathway. These insights enhance our understanding of AF pathogenesis and position ANP as a potential therapeutic agent for treating atrial fibrosis.

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Section: Discussionmentioning

confidence: 99%

Targeting myocardial inflammation: investigating the therapeutic potential of atrial natriuretic peptide in atrial fibrosis

Zhu,

Li,

Bai

et al. 2024

Mol Biol Rep

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“…The TN64 antibody is directed against the FNIII - like repeats 1-5 (TNfnIII 1-5) of TNC, and has been observed to prevent fibroblast-mediated cartilage destruction. The TN64 antibody was evaluated in collagen-induced arthritis in BALB/c mice, and TN64 was found to prevent the induction of arthritis by downregulation of TNF-α, IL-6, IL-10, IL-12, and IFN-γ ( 38 ). Both full-length TNC and the FBG domain induced synthesis of IL-6 in synovial fibroblasts ( 35 ).…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Tenascin-C in Osteoarthritis and Rheumatoid Arthritis

2020

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Tenascin-C (TNC) is a large multimodular glycoprotein of the extracellular matrix that consists of four distinct domains. Emerging evidence suggests that TNC may be involved in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In this review, we summarize the current understanding of the role of TNC in cartilage and in synovial biology, across both OA and RA. TNC is expressed in association with the development of articular cartilage; the expression decreases during maturation of chondrocytes and disappears almost completely in adult articular cartilage. TNC expression is increased in diseased cartilage, synovium, and synovial fluid in OA and RA. In addition, elevated circulating TNC levels have been detected in the blood of RA patients. Thus, TNC could be used as a novel biochemical marker for OA and RA, although it has no specificity as a biochemical marker for these joint disorders. In a post-traumatic OA model of aged joints, TNC deficiency was shown to enhance cartilage degeneration. Treatment with TNC domains results in different, domain-specific effects, which are also dose-dependent. For instance, some TNC fragments including the fibrinogen-like globe domain might function as endogenous inducers of synovitis and cartilage matrix degradation through binding with toll-like receptor-4, while full-length TNC promotes cartilage repair and prevents the development of OA without exacerbating synovitis. The TNC peptide TNIIIA2 also prevents cartilage degeneration without causing synovial inflammation. The clinical significance of TNC effects on cartilage and synovium is unclear and understanding the clinical significance of TNC is not straightforward.

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“…72 The FN-III domains bind TGF-β, PDGF and other growth factors. 73 TN-C supports inflammation 74 and stimulates the migration of human dermal fibroblasts. 75 The response of fibroblasts from TN-C-deficient mice to TGF-β is decreased.…”

Section: Fibronectinmentioning

confidence: 99%

Role of fibronectin in chronic venous diseases: A review

Kanta

Zavaďáková

2020

Vasc Med

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Fibronectin (FN) circulating in the blood and produced by cells provides the basis of the extracellular matrix (ECM) formed in healing acute wounds. The time-dependent deposition of FN by macrophages, its synthesis by fibroblasts and myofibroblasts, and later degradation in the remodeled granulation tissue are a prerequisite for successful healing of wounds. However, the pattern of FN expression and deposition in skin lesions is disturbed. The degradation of the ECM components including FN in varicose veins prevails over ECM synthesis and deposition. FN is inconspicuous in the fibrotic lesions in lipodermatosclerosis, while tenascin-C containing FN-like peptide sequences are prominent. FN is produced in large amounts by fibroblasts at the edge of venous ulcers but FN deposition at the wound bed is impaired. Both the proteolytic environment in the wounds and the changed function of the ulcer fibroblasts may be responsible for the poor healing of venous ulcers. The aim of this review is to describe the current knowledge of FN pathophysiology in chronic venous diseases. In view of the fact that FN plays a crucial role in organizing the ECM, further research focused on FN metabolism in venous diseases may bring results applicable to the treatment of the diseases.

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Amelioration of collagen antibody induced arthritis in mice by an antibody directed against the fibronectin type III repeats of tenascin-C

Cited by 10 publications

References 40 publications

Targeting myocardial inflammation: investigating the therapeutic potential of atrial natriuretic peptide in atrial fibrosis

Targeting myocardial inflammation: investigating the therapeutic potential of atrial natriuretic peptide in atrial fibrosis

Tenascin-C in Osteoarthritis and Rheumatoid Arthritis

Role of fibronectin in chronic venous diseases: A review

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