MitomiRs in human inflamm-aging: A hypothesis involving miR-181a, miR-34a and miR-146a

Rippo, Maria Rita; Olivieri, Fabiola; Monsurró, Vladia; Prattichizzo, Francesco; Albertini, Maria Cristina; Procopio, Antonio Domenico

doi:10.1016/j.exger.2014.03.002

Cited by 177 publications

(140 citation statements)

References 84 publications

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“…The deregulated expression of miRNAs such as miR-34 and miR-106 (our unpublished data), known to activate TGFb1 signaling pathway (40) and in relation with inflammaging (41), are in agreement with our hypothesis. The high inflammatory context in which primary myelofibrosis is developing could therefore promote epigenetic alterations of primary myelofibrosis patient's stroma, resulting in MSC imprinting.…”

Section: Discussionsupporting

confidence: 90%

Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis

et al. 2015

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Primary myelofibrosis is a myeloproliferative neoplasm that is a precursor to myeloid leukemia. Dysmegakaryopoiesis and extramedullary hematopoiesis characterize primary myelofibrosis, which is also associated with bone marrow stromal alterations marked by fibrosis, neoangiogenesis, and osteomyelosclerosis. In particular, contributions to primary myelofibrosis from mesenchymal stromal cells (MSC) have been suggested by mouse studies, but evidence in humans remains lacking. In this study, we show that bone marrow MSCs from primary myelofibrosis patients exhibit unique molecular and functional abnormalities distinct from other myeloproliferative neoplasms and these abnormalities are maintained stably ex vivo in the absence of leukemic cells. Primary myelofibrosis-MSC overexpressed heparin-binding cytokines, including proinflammatory TGFb1 and osteogenic BMP-2, as well as glycosaminoglycans such as heparan sulfate and chondroitin sulfate. Transcriptome and functional analyses revealed alterations in MSC differentiation characterized by an increased osteogenic potential and a TGFb1 signaling signature. Accordingly, phospho-Smad2 levels were intrinsically increased in primary myelofibrosis-MSC along with enhanced expression of the master bone regulator RUNX2, while inhibition of the endogenous TGFb1 receptor TGFbR1 impaired osteogenic differentiation in these MSCs. Taken together, our results define the source of a critical osteogenic function in primary myelofibrosis that supports its pathophysiology, suggesting that combined targeting of both the hematopoietic and stromal cell compartments in primary myelofibrosis patients may heighten therapeutic efficacy. Cancer Res; 75(22); 4753-65. Ó2015 AACR.

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Section: Discussionsupporting

confidence: 90%

Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis

et al. 2015

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“…These so-called mitomiRs are different according to species and cell types, and their modulation is involved in inflammation and age-related diseases. 56 Although miR-125b is considered a mitomiR in human skeletal muscular cells, 57 we could not detect it in mitochondria isolated from human monocytes (data not shown).…”

Section: Discussionmentioning

confidence: 84%

miR-125b controls monocyte adaptation to inflammation through mitochondrial metabolism and dynamics

Duroux-Richard

Roubert

Ammari

et al. 2016

Blood

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Key Points• miR-125b reduces mitochondrial respiration and promotes elongation of mitochondrial network through BIK and MTP18 silencing, respectively. • The miR-125b/BIK/MTP18 axis promotes adaptation of monocytes to inflammation.Metabolic changes drive monocyte differentiation and fate. Although abnormal mitochondria metabolism and innate immune responses participate in the pathogenesis of many inflammatory disorders, molecular events regulating mitochondrial activity to control life and death in monocytes remain poorly understood. We show here that, in human monocytes, microRNA-125b (miR-125b) attenuates the mitochondrial respiration through the silencing of the BH3-only proapoptotic protein BIK and promotes the elongation of the mitochondrial network through the targeting of the mitochondrial fission process 1 protein MTP18, leading to apoptosis. Proinflammatory activation of monocyte-derived macrophages is associated with a concomitant increase in miR-125b expression and decrease in BIK and MTP18 expression, which lead to reduced oxidative phosphorylation and enhanced mitochondrial fusion. In a chronic inflammatory systemic disorder, CD14 1 blood monocytes display reduced miR-125b expression as compared with healthy controls, inversely correlated with BIK and MTP18 messenger RNA expression. Our findings not only identify BIK and MTP18 as novel targets for miR-125b that control mitochondrial metabolism and dynamics, respectively, but also reveal a novel function for miR-125b in regulating metabolic adaptation of monocytes to inflammation. Together, these data unravel new molecular mechanisms for a proapoptotic role of miR-125b in monocytes and identify potential targets for interfering with excessive inflammatory activation of monocytes in inflammatory disorders. (Blood. 2016;128(26): 3125-3136)

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“…Upon validation by qRT-PCR, miR-146a, miR-92a-2*, miR-147, miR-21 and miR-20 were shown to significantly increase at 4 and 15 weeks, while miR-181a significantly decreased upon cigarette smoke exposure. Of interest, both miR-146a and miR-181a have been linked to "inflammaging", an ageing-related state characterised by systemic chronic inflammation [42]. Since the authors also found significantly increased serum levels of miR-21 and decreased miR-181a expression in heavy smokers and COPD patients compared with healthy controls [21], they suggested that a high ratio of serum miR-21 to miR-181a expression may be a risk factor for the development of COPD and can be associated with the risk of developing COPD in heavy smokers.…”

Section: Introductionmentioning

confidence: 99%

Unravelling the complexity of COPD by microRNAs: it's a small world after all

et al. 2015

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Chronic obstructive pulmonary disease (COPD) is a progressive lung disease and is currently the fourth leading cause of death worldwide. Chronic inflammation and repair processes in the small airways are characteristic of COPD. Despite extensive efforts from researchers and industry, there is still no cure for COPD, hence an urgent need for new therapeutic alternatives. MicroRNAs are such an option; they are small noncoding RNAs involved in gene regulation. Their importance has been shown with respect to maintaining the balance between health and disease. Although previous reviews have discussed the expression of microRNAs related to lung disease, a detailed discussion regarding the function of differential miRNA expression in the pathogenesis of COPD is lacking.In this review we link the expression of microRNAs to different features of COPD and explain their importance in the pathogenesis of this disease. We further discuss their potential to contribute to the development of future therapeutic strategies. @ERSpublications Complexity of miRNAs in COPD: an up-to-date overview of the role of miRNAs in the different features of COPD http://ow.ly/Pk4FP

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MitomiRs in human inflamm-aging: A hypothesis involving miR-181a, miR-34a and miR-146a

Cited by 177 publications

References 84 publications

Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis

Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis

miR-125b controls monocyte adaptation to inflammation through mitochondrial metabolism and dynamics

Unravelling the complexity of COPD by microRNAs: it's a small world after all

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