Elevated protein arginine methyltransferase 1 expression regulates fibroblast motility in pulmonary fibrosis

Zakrzewicz, Dariusz; Zakrzewicz, Anna; Didiášová, Miroslava; Korencak, Marek; Kosanovic, Djuro; Schermuly, Ralph Theo; Markart, Philipp; Wygrecka, Małgorzata

doi:10.1016/j.bbadis.2015.09.008

Cited by 16 publications

(12 citation statements)

References 41 publications

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“…Zakrzewicz et al . have recently reported that there is elevated expression of PRMT1 in the lungs of patients with idiopathic pulmonary fibrosis or IPF35. This finding is in keeping with our observation because we have previously shown that IFN-γ antagonizes the pathogenesis of IPF by inducing CIITA to repress collagen type I transcription363738.…”

Section: Discussionsupporting

confidence: 92%

Protein arginine methyltransferase 1 (PRMT1) represses MHC II transcription in macrophages by methylating CIITA

Fan

et al. 2017

Sci Rep

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Efficient presentation of alien antigens triggers activation of T lymphocytes and robust host defense against invading pathogens. This pathophysiological process relies on the expression of major histocompatibility complex (MHC) molecules in antigen presenting cells such as macrophages. Aberrant MHC II transactivation plays a crucial role in the pathogenesis of atherosclerosis. Class II transactivator (CIITA) mediates MHC II induction by interferon gamma (IFN-γ). CIITA activity can be fine-tuned at the post-translational level, but the mechanisms are not fully appreciated. We investigated the role of protein arginine methyltransferase 1 (PRMT1) in this process. We report here that CIITA interacted with PRMT1. IFN-γ treatment down-regulated PRMT1 expression and attenuated PRMT1 binding on the MHC II promoter. Over-expression of PRMT1 repressed MHC II promoter activity while PRMT1 depletion enhanced MHC II transactivation. Mechanistically, PRMT1 methylated CIITA and promoted CIITA degradation. Therefore, our data reveal a previously unrecognized role for PRMT1 in suppressing CIITA-mediated MHC II transactivation.

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Section: Discussionsupporting

confidence: 92%

Protein arginine methyltransferase 1 (PRMT1) represses MHC II transcription in macrophages by methylating CIITA

Fan

et al. 2017

Sci Rep

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“…Previous studies have shown that IL-4 promotes PRMT1 expression in lung fibroblasts and airway epithelial cells. 16,28 In the present study, IL-4 also upregulated the gene and protein expression of PRMT1 in nasal epithelial cells. Interestingly, HDM synergized with IL-4 to enhance PRMT1 expression and its nuclear localization in the cells, which suggests that allergens might cooperate with IL-4 to regulate PRMT1 expression.…”

Section: Discussionsupporting

confidence: 65%

“…25 In lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis, PRMT1 is predominantly localized in the nucleus and moderately expressed in the cytoplasm. 28 In the present study, we found strong PRMT1 expression in the nuclei of nasal epithelial cells of patients and mice with AR, although weak to moderate PRMT1 expression was still observed in the cytoplasm. Moreover, confocal microscopy observations showed that the nuclear expression of PRMT1 in RPMI 2650 cells was enhanced in response to HDM and rIL-4 and thus supported this hypothesis.…”

Section: Discussionsupporting

confidence: 55%

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Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines

Park

Choi

Lee

et al. 2021

Journal of Allergy and Clinical Immunology

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Background: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. Objective: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). Methods: The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. Results: PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1 1/2 AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of T H 2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinasedependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. Conclusions: PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR. (J

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“…Previous studies showed that over 90% of the arginine methylation in mammalian cells was produced by PRMT1 catalysis [9]. Furthermore, the disordered expression of PRMT1 is associated with a variety of human diseases including pulmonary fibrosis [10], cardiovascular diseases [11], diabetes, renal diseases [12] and cancer in particular [13,14,15,16]. Overexpression of PRMT1 can promote the growth, survival, metastasis and invasion of tumor cells [17].…”

Section: Introductionmentioning

confidence: 99%

The Development of Tetrazole Derivatives as Protein Arginine Methyltransferase I (PRMT I) Inhibitors

Sun

Wang

Yang

et al. 2019

IJMS

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Protein arginine methyltransferase 1 (PRMT1) can catalyze protein arginine methylation by transferring the methyl group from S-adenosyl-L-methionine (SAM) to the guanidyl nitrogen atom of protein arginine, which influences a variety of biological processes. The dysregulation of PRMT1 is involved in a diverse range of diseases, including cancer. Therefore, there is an urgent need to develop novel and potent PRMT1 inhibitors. In the current manuscript, a series of 1-substituted 1H-tetrazole derivatives were designed and synthesized by targeting at the substrate arginine-binding site on PRMT1, and five compounds demonstrated significant inhibitory effects against PRMT1. The most potent PRMT1 inhibitor, compound 9a, displayed non-competitive pattern with respect to either SAM or substrate arginine, and showed the strong selectivity to PRMT1 compared to PRMT5, which belongs to the type II PRMT family. It was observed that the compound 9a inhibited the functions of PRMT1 and relative factors within this pathway, and down-regulated the canonical Wnt/β-catenin signaling pathway. The binding of compound 9a to PRMT1 was carefully analyzed by using molecular dynamic simulations and binding free energy calculations. These studies demonstrate that 9a was a potent PRMT1 inhibitor, which could be used as lead compound for further drug discovery.

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Elevated protein arginine methyltransferase 1 expression regulates fibroblast motility in pulmonary fibrosis

Abstract: PRMT1 can contribute to the development of pulmonary fibrosis by regulating fibroblast activities. Thus, interference with its expression and/or activity may provide a novel therapeutic option for patients with IPF.

Cited by 16 publications

References 41 publications

Protein arginine methyltransferase 1 (PRMT1) represses MHC II transcription in macrophages by methylating CIITA

Protein arginine methyltransferase 1 (PRMT1) represses MHC II transcription in macrophages by methylating CIITA

Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines

The Development of Tetrazole Derivatives as Protein Arginine Methyltransferase I (PRMT I) Inhibitors

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