Pirfenidone modifies hepatic miRNAs expression in a model of MAFLD/NASH

Escutia-Gutiérrez, Rebeca; Rodríguez-Sanabria, J. Samael; Monraz-Méndez, C. Alejandra; García-Bañuelos, Jesús; Santos, Arturo; Sandoval-Rodríguez, Ana; Armendáriz‐Borunda, Juan

doi:10.1038/s41598-021-91187-2

Cited by 19 publications

(12 citation statements)

References 73 publications

(86 reference statements)

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“…Similarly, our data showed a higher hepatic miR-34a-5p expression in MAFLD model, while MO administration lessens its induction. In addition, a decrease in the expression of miR-34a-5p and an increase in its target genes Sirt1 and Ppara have been reported when PFD was used against MAFLD development in a rodent model [ 53 ]; these results are in accordance with our data.…”

Section: Discussionsupporting

confidence: 93%

Moringa oleifera Improves MAFLD by Inducing Epigenetic Modifications

et al. 2022

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Background and aims. Metabolic Associated Fatty Liver Disease (MAFLD) encompasses a spectrum of diseases from simple steatosis to nonalcoholic steatohepatitis (NASH). Here, we investigated the hepatoprotective role of Moringa oleifera aqueous extract on hepatic miRNAs, genes and protein expression, as well as histological and biochemical parameters in an experimental model of NASH. Methods. Male C57BL/6J mice were fed with a high fat diet (HFD, 60% lipids, 42 gr/L sugar in water) for 16 weeks. Moringa extract was administered via gavage during the final 8 weeks. Insulin Tolerance Test (ITT) and HOMA-IR were calculated. Serum levels of insulin, resistin, leptin and PAI-1 and hepatic expression of miR-21a-5p, miR-103-3p, miR-122-5p, miR-34a-5p and SIRT1, AMPKα and SREBP1c protein were evaluated. Alpha-SMA immunohistochemistry and hematoxylin-eosin, Masson’s trichrome and sirius red staining were made. Hepatic transcriptome was analyzed using microarrays. Results. Animals treated with Moringa extract improved ITT and decreased SREBP1c hepatic protein, while SIRT1 increased. Hepatic expression of miR-21a-5p, miR-103-3p and miR-122-5p, miR34a-5p was downregulated. Hepatic histologic analysis showed in Moringa group (HF + MO) a significant decrease in inflammatory nodules, macro steatosis, fibrosis, collagen and αSMA reactivity. Analysis of hepatic transcriptome showed down expression of mRNAs implicated in DNA response to damage, endoplasmic reticulum stress, lipid biosynthesis and insulin resistance. Moringa reduced insulin resistance, de novo lipogenesis, hepatic inflammation and ER stress. Conclusions. Moringa prevented progression of liver damage in a model of NASH and improved biochemical, histological and hepatic expression of genes and miRNAs implicated in MAFLD/NASH development.

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Section: Discussionsupporting

confidence: 93%

Moringa oleifera Improves MAFLD by Inducing Epigenetic Modifications

et al. 2022

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“…It has been demonstrated that the miR-122 expression levels rise in the mouse liver over the course of development, peaking immediately before birth. Therefore, the loss of miR-122 expression in HCC may signify either a reversal of differentiation or a block at a less differentiated state [ 10 , 24 ]. Accordingly, this study was designed as an attempt to restore the normal miRNA expression pattern of an oncogene; miR-221, and a tumor suppressor miRNA; miR-221, that had been disrupted during the process of hepatocarcinogenesis and to explore whether this therapeutic strategy would be more effective than a single miRNA restoration approach.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-122 mimic/microRNA-221 inhibitor combination as a novel therapeutic tool against hepatocellular carcinoma

Hassan

Elzallat

Aboushousha

et al. 2023

Non-coding RNA Research

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“…Functions of miR-34a may differ depending on liver diseases, animal models, or the kinds of liver cells. 20 Similarly, acute attenuation of angiogenesis is good for ALD but may have dire consequences in the future. Since hepatic cells communicate with each other and orchestrate to maintain liver homeostasis during liver injury, miR-34a could play a vital role only in specific liver cells, such as hepatic macrophages and endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

miR-34a regulates macrophage-associated inflammation and angiogenesis in alcohol-induced liver injury

Wan

Slevin

Koyama

et al. 2023

Hepatology Communications

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Background: Alcohol-associated liver disease (ALD) is a syndrome of progressive inflammatory liver injury and vascular remodeling associated with long-term heavy intake of ethanol. Elevated miR-34a expression, macrophage activation, and liver angiogenesis in ALD and their correlation with the degree of inflammation and fibrosis have been reported. The current study aims to characterize the functional role of miR-34a-regulated macrophage- associated angiogenesis during ALD. Methods & Results: We identified that knockout of miR-34a in 5 weeks of ethanol-fed mice significantly decreased the total liver histopathology score and miR-34a expression, along with the inhibited liver inflammation and angiogenesis by reduced macrophage infiltration and CD31/VEGF-A expression. Treatment of murine macrophages (RAW 264.7) with lipopolysaccharide (20 ng/mL) for 24 h significantly increased miR-34a expression, along with the enhanced M1/M2 phenotype changes and reduced Sirt1 expression. Silencing of miR-34a significantly increased oxygen consumption rate (OCR) in ethanol treated macrophages, and decreased lipopolysaccharide-induced activation of M1 phenotypes in cultured macrophages by upregulation of Sirt1. Furthermore, the expressions of miR-34a and its target Sirt1, macrophage polarization, and angiogenic phenotypes were significantly altered in isolated macrophages from ethanol-fed mouse liver specimens compared to controls. TLR4/miR-34a knockout mice and miR-34a Morpho/AS treated mice displayed less sensitivity to alcohol-associated injury, along with the enhanced Sirt1 and M2 markers in isolated macrophages, as well as reduced angiogenesis and hepatic expressions of inflammation markers MPO, LY6G, CXCL1, and CXCL2. Conclusion: Our results show that miR-34a-mediated Sirt1 signaling in macrophages is essential for steatohepatitis and angiogenesis during alcohol-induced liver injury. These findings provide new insight into the function of microRNA-regulated liver inflammation and angiogenesis and the implications for reversing steatohepatitis with potential therapeutic benefits in human alcohol-associated liver diseases.

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Pirfenidone modifies hepatic miRNAs expression in a model of MAFLD/NASH

Cited by 19 publications

References 73 publications

Moringa oleifera Improves MAFLD by Inducing Epigenetic Modifications

Moringa oleifera Improves MAFLD by Inducing Epigenetic Modifications

MicroRNA-122 mimic/microRNA-221 inhibitor combination as a novel therapeutic tool against hepatocellular carcinoma

miR-34a regulates macrophage-associated inflammation and angiogenesis in alcohol-induced liver injury

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