The co-activator-associated arginine methyltransferase 1 (CARM1) gene is overexpressed in type 2 diabetes

Porta, Massimo; Amione, Cristina; Barutta, Federica; Fornengo, Paolo; Merlo, Stefano; Gruden, Gabriella; Albano, Luigi; Ciccarelli, Marco; Ungaro, Paola; Durazzo, Marilena; Béguinot, Francesco; Berchialla, Paola; Cavallo, Franco; Trento, Marina

doi:10.1007/s12020-018-1740-z

Cited by 18 publications

(12 citation statements)

References 46 publications

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“…PRMT4 is widely expressed in tissues throughout the body and overexpressed in human patients with cancers and T2DM. 14,15 In our study, increased PRMT4 expression was observed in the WAT of STZ-induced mice. However, PRMT4 expression varies among different tissues in STZinduced models of diabetes.…”

Section: Discussionsupporting

confidence: 61%

“…14 In patients with T2DM, PRMT4 is overexpressed in the white blood cells. 15 A previous study has shown that this enzyme is also overexpressed in retinal pigment epithelial cells of rats with T1DM, where it induces apoptosis in these cells. 16,17 PRMT4 regulates various cellular processes, such as DNA repair, transcriptional coactivation, mRNA splicing, and protein translocation.…”

Section: Introductionmentioning

confidence: 95%

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<p>Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice</p>

Peng

Zeng

et al. 2020

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Purpose: Hypertriglyceridemia is considered to be driven by increased lipolysis in type 1 diabetes mellitus (T1DM). However, information regarding the transcriptional circuitry that governs lipolysis remains incomplete in T1DM. Protein arginine methyltransferase 4 (PRMT4), a transcriptional coactivation factor, promotes autophagy and may play an important role in lipolysis. We wonder whether activated lipolysis in T1DM is regulated by PRMT4. Materials and Methods: Recombinant adeno-associated virus was adopted to overexpress PRMT4 in adipose tissue of mice. Streptozotocin (150 mg/kg) was injected intraperitoneally into mice to induce T1DM. Plasma insulin, triglycerides, free fatty acids (FFAs) levels were determined using commercial assay kits. Differentiated adipocytes were applied to verify the regulation of PRMT4 on lipolysis. Results: Elevated serum triglycerides and FFAs were observed in PRMT4-overexpressed T1DM mice. We also observed that PRMT4 over-expression induced the decrease of fat pads weights and adipocyte sizes. Moreover, expression levels of lipolysis-related molecules, including ATGL, HSL, and MAGL, and HSL phosphorylation levels were increased in PRMT4-overexpressed mice when compared to those of control mice. In vitro, PRMT4 promoted FFAs release and activated HSL phosphorylation, whereas PRMT4 knockdown inhibited these processes. Conclusion: PRMT4 promotes lipolysis and increases serum triglyceride in T1DM.

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Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 95%

<p>Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice</p>

Peng

Zeng

et al. 2020

DMSO

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“…Co-activator-associated arginine methyltransferase 1 (CARM1) is a coactivator of transcriptional activation and forms homodimers, which is necessary for catalytic activity (Chen et al 1999;Higashimoto et al, 2007). Recently, CARM1 was found to be increased in patients with diabetes (Porta et al, 2019). Additionally, CARM1 is elevated and participates in the regulation of high-glucose (HG) treated human retinal pigment epithelial cells (Kim et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

MiR-542-5p regulates the progression of diabetic retinopathy by targeting CARM1

Guo

Nulahou

et al. 2020

Acta Biochim Pol

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Diabetic retinopathy (DR), as the most frequent microvascular complication of diabetes mellitus (DM), causes vision loss and blindness in adults worldwide with increasing incidence. MicroRNAs (miRNAs) are involved in the regulation of DR. However, the role of miR-542-5p is still unknown. Here, we demonstrate that miR-542-5p is down-regulated in patients with DR and in high-glucose (HG)-treated retinal pigment epithelial cells. Moreover, miR-542-5p overexpression inhibits apoptosis in retinal pigment epithelial cells exposed to HG. The interaction between miR-542-5p and co-activator-associated arginine methyltransferase 1 (CARM1) is confirmed. MiR-542-5p mimics decrease the CARM1 level and miR-542-5p inhibitor increases the CARM1 level. Additionally, CARM1 overexpression promotes the miR-542-5p-mediated apoptosis in HG-treated retinal pigment epithelial cells. In summary, the data suggest that miR-542-5p may suppress apoptosis in retinal pigment epithelial cells via targeting CARM1, which provides a new therapeutic target for the treatment of patients with DR.

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“…Compared to lysine modification, there is much less information regarding histone arginine methylation in diabetic complications, including wound healing. A few studies have shown that PRMTs are involved in insulin secretion in β-cells and some are overexpressed in diabetes (122)(123)(124). However, PRMTs can, not only methylate histones, but also non-histone proteins (121).…”

Section: Histone Modificationsmentioning

confidence: 99%

Targeting epigenetic mechanisms in diabetic wound healing

Dekker

Davis

Kunkel

et al. 2019

Translational Research

161

121

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Impaired wound healing is a major secondary complication of type 2 diabetes that often results in limb loss and disability. Normal tissue repair progresses through discrete phases including hemostasis, inflammation, proliferation, and remodeling. In diabetes, normal progression through these phases is impaired resulting in a sustained inflammatory state and dysfunctional epithelialization in the wound. Due to their plasticity, macrophages play a critical role in the transition from the inflammation phase to the proliferation phase. Diabetes disrupts macrophage function by impairing monocyte recruitment to the wound, reducing phagocytosis, and prohibiting the transition of inflammatory macrophages to an anti-inflammatory state. Diabetes also impedes keratinocyte and fibroblast function during the later phases resulting in impaired epithelialization of the wound. Several recent studies suggest that altered epigenetic regulation of both immune and structural cells in wounds may influence cell phenotypes and healing, particularly in pathologic states, such as diabetes. Specifically, it has been shown that macrophage plasticity during wound repair is partly regulated epigenetically and that diabetes alters this epigenetic regulation and contributes to a sustained inflammatory state. Epigenetic regulation is also known to regulate keratinocyte and fibroblast function during wound repair. In this review, we provide an introduction to the epigenetic mechanisms that regulate tissue repair and highlight recent findings that demonstrate how epigenetic events are altered during the course of diabetic wound healing.

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The co-activator-associated arginine methyltransferase 1 (CARM1) gene is overexpressed in type 2 diabetes

Abstract: Increased CARM1 expression in type 2 diabetes suggests that epigenetic mechanisms are altered in human diabetes. The impact of lifestyle and pharmacological treatment on regulation of this enzyme should be further investigated.

Cited by 18 publications

References 46 publications

<p>Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice</p>

<p>Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice</p>

MiR-542-5p regulates the progression of diabetic retinopathy by targeting CARM1

Targeting epigenetic mechanisms in diabetic wound healing

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