The C0-C1f Region of Cardiac Myosin Binding Protein-C Induces Pro-Inflammatory Responses in Fibroblasts via TLR4 Signaling

Yogeswaran, Athiththan; Troidl, Christian; McNamara, James W.; Wilhelm, Jochen; Truschel, Theresa; Widmann, Laila; Aslam, Muhammad; Hamm, Christian W.; Sadayappan, Sakthivel; Lipps, Christoph

doi:10.3390/cells10061326

Cited by 5 publications

(4 citation statements)

References 46 publications

(77 reference statements)

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“…Due to serine is a neutral amino acid carry in hydroxyl functioning, the loss of positive charge caused by deamination of arginine can modulate the electrostatic interaction with partner proteins. There is no strong evidence regrading the possible role of myosin-binding protein C in RA, but the C0-C1f region of MyBP-C, released after the cleavage by µ-calpain, exhibits pro-inflammatory activity though the activation of macrophages and fibroblasts [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Dynamics Study of Citrullinated Proteins Associated with the Development of Rheumatoid Arthritis

et al. 2022

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Biological activity regulation by protein post-translational modification (PTM) is critical for cell function, development, differentiation, and survival. Dysregulation of PTM proteins is present in various pathological conditions, including rheumatoid arthritis (RA). RA is a systemic autoimmune disease that primarily affects joints, and there are three main types of protein PTMs associated with the development of this disease, namely, glycosylation, citrullination, and carbamylation. Glycosylation is important for the processing and presentation of antigen fragments on the cell surface and can modulate immunoglobulin activity. The citrullination of autoantigens is closely associated with RA, as evidenced by the presence of antibodies specific to citrullinated proteins in the serum of patients. Carbamylation and dysregulation have recently been associated with RA development in humans.In this study, we performed an overview analysis of proteins with post-translational modifications associated with the development of RA adverted in peer-reviewed scientific papers for the past 20 years. As a result of the search, a list of target proteins and corresponding amino acid sequences with PTM in RA was formed. Structural characteristics of the listed modified proteins were extracted from the Protein Data Bank. Then, molecular dynamics experiments of intact protein structures and corresponding structures with PTMs were performed regarding structures in the list announced in the ProtDB service. This study aimed to conduct a molecular dynamics study of intact proteins and proteins, including post-translational modification and protein citrullination, likely associated with RA development. We observed another exhibition of the fundamental physics concept, symmetry, at the submolecular level, unveiled as the autonomous repetitions of outside the protein structural motif performance globule corresponding to those in the whole protein molecule.

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Section: Discussionmentioning

confidence: 99%

Molecular Dynamics Study of Citrullinated Proteins Associated with the Development of Rheumatoid Arthritis

et al. 2022

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“…This could be explained in several ways. First, cMyBP-C is sensitive to proteolysis during myocardial infarction and could be a potential earlier biomarker for heart attack ( 45 – 47 ). Thus, patients with MYBPC3 Δ25bp may not have enough wild-type cMyBP-C turnover, resulting in haploinsufficiency ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

South Asian-Specific MYBPC3Δ25bp Deletion Carriers Display Hypercontraction and Impaired Diastolic Function Under Exercise Stress

Bazrafshan

Sibilia

Girgla

et al. 2021

Front. Cardiovasc. Med.

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Background: A 25-base pair (25bp) intronic deletion in the MYBPC3 gene enriched in South Asians (SAs) is a risk allele for late-onset left ventricular (LV) dysfunction, hypertrophy, and heart failure (HF) with several forms of cardiomyopathy. However, the effect of this variant on exercise parameters has not been evaluated.Methods: As a pilot study, 10 asymptomatic SA carriers of the MYBPC3Δ25bp variant (52.9 ± 2.14 years) and 10 age- and gender-matched non-carriers (NCs) (50.1 ± 2.7 years) were evaluated at baseline and under exercise stress conditions using bicycle exercise echocardiography and continuous cardiac monitoring.Results: Baseline echocardiography parameters were not different between the two groups. However, in response to exercise stress, the carriers of Δ25bp had significantly higher LV ejection fraction (%) (CI: 4.57 ± 1.93; p < 0.0001), LV outflow tract peak velocity (m/s) (CI: 0.19 ± 0.07; p < 0.0001), and higher aortic valve (AV) peak velocity (m/s) (CI: 0.103 ± 0.08; p = 0.01) in comparison to NCs, and E/A ratio, a marker of diastolic compliance, was significantly lower in Δ25bp carriers (CI: 0.107 ± 0.102; p = 0.038). Interestingly, LV end-diastolic diameter (LVIDdia) was augmented in NCs in response to stress, while it did not increase in Δ25bp carriers (CI: 0.239 ± 0.125; p = 0.0002). Further, stress-induced right ventricular systolic excursion velocity s' (m/s), as a marker of right ventricle function, increased similarly in both groups, but tricuspid annular plane systolic excursion increased more in carriers (slope: 0.008; p = 0.0001), suggesting right ventricle functional differences between the two groups.Conclusions: These data support that MYBPC3Δ25bp is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.

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“…The former encoding gene is located in the second exon region of human chromosome 5, while the latter is located in the q24–26 region of human chromosome 10 [ 65 ]. In myocardial fibrosis caused by myocardial injury, the N-terminal peptide C0–C1f of the myocardial binding protein C can activate the NF-κB pathway through TLR4 to cause inflammation and delay TGF-β-induced fibroblast activation; miR-146 can inhibit the C0-C1f function [ 66 ]. These results suggest that miR-146 also plays an important role in fibrosis.…”

Section: Ncrna Activates or Inhibits Different Signaling Pathways To ...mentioning

confidence: 99%

Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis

Zhang

Zhou

Wen

et al. 2023

IJMS

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Myofibroblasts escape apoptosis and proliferate abnormally under pathological conditions, especially fibrosis; they synthesize and secrete a large amount of extracellular matrix (ECM), such as α-SMA and collagen, which leads to the distortion of organ parenchyma structure, an imbalance in collagen deposition and degradation, and the replacement of parenchymal cells by fibrous connective tissues. Fibroblast to myofibroblast transition (FMT) is considered to be the main source of myofibroblasts. Therefore, it is crucial to explore the influencing factors regulating the process of FMT for the prevention, treatment, and diagnosis of FMT-related diseases. In recent years, non-coding RNAs, including microRNA, long non-coding RNAs, and circular RNAs, have attracted extensive attention from scientists due to their powerful regulatory functions, and they have been found to play a vital role in regulating FMT. In this review, we summarized ncRNAs which regulate FMT during fibrosis and found that they mainly regulated signaling pathways, including TGF-β/Smad, MAPK/P38/ERK/JNK, PI3K/AKT, and WNT/β-catenin. Furthermore, the expression of downstream transcription factors can be promoted or inhibited, indicating that ncRNAs have the potential to be a new therapeutic target for FMT-related diseases.

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The C0-C1f Region of Cardiac Myosin Binding Protein-C Induces Pro-Inflammatory Responses in Fibroblasts via TLR4 Signaling

Cited by 5 publications

References 46 publications

Molecular Dynamics Study of Citrullinated Proteins Associated with the Development of Rheumatoid Arthritis

Molecular Dynamics Study of Citrullinated Proteins Associated with the Development of Rheumatoid Arthritis

South Asian-Specific MYBPC3Δ25bp Deletion Carriers Display Hypercontraction and Impaired Diastolic Function Under Exercise Stress

Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis

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