Monocyte chemoattractant protein-induced protein 1 impairs adipogenesis in 3T3-L1 cells

Lipert, Barbara; Węgrzyn, Paulina; Sell, Henrike; Eckel, Jürgen; Winiarski, Marek; Budzyński, Andrzej; Matłok, Maciej; Kotlinowski, Jerzy; Ramage, Lynne; Małecki, Maciej T.; Wilk, Wacław; Mituś, Jerzy; Jura, Jolanta

doi:10.1016/j.bbamcr.2014.01.001

Cited by 34 publications

(44 citation statements)

References 25 publications

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“…Our previous and present results indicate that MCPIP1 represses expression of C/EBPβ in mouse and humans [17]. This brings new insight into understanding of regulatory networks and orchestrated response to IL-1 and IL-6 cytokines.…”

Section: Discussionsupporting

confidence: 64%

MCPIP1, alias Regnase-1 binds and cleaves mRNA of C/EBPβ

et al. 2017

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CCAAT/enhancer-binding protein beta (C/EBPβ) is a transcription factor controlling a broad range of genes essential for homeostasis, including genes related to immune functions, inflammation, metabolism and growth. Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) also called as Regnase-1 is an RNase and has been shown to decrease the stability of short-lived transcripts coding for inflammation-related proteins, including IL-1β, IL-6, IL-2, IL-8, IL-12b, IER-3, c-Rel. We found previously that the half-life of the C/EBPβ transcript is regulated by MCPIP. To understand the mechanism driving down-regulation of C/EBPβ by MCPIP1, we applied an in vitro cleavage assay, followed by a luciferase-reporter assay and RNA immunoprecipitation (RIP). We demonstrated that MCPIP1 recognizes regions of the 3’UTR of C/EBPβ mRNA and promotes its decay by introducing direct endonucleolytic cleavage.

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Section: Discussionsupporting

confidence: 64%

MCPIP1, alias Regnase-1 binds and cleaves mRNA of C/EBPβ

et al. 2017

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“…The fact that MCPIP1 is downregulated under hypoxic conditions has an important impact on many cellular processes. MCPIP1 influences the levels of many transcripts coding for proinflammatory cytokines (IL-6, IL-1, and many others), transcription factors (NFkappaB, C/EBPbeta), signaling proteins (JNK, Akt/mTor) [8–13, 36–38]. The whole list of targets is not known yet; thus, it is difficult to predict which other cellular processes are altered by diminished level of MCPIP1.…”

Section: Discussionmentioning

confidence: 99%

MCPIP1 contributes to clear cell renal cell carcinomas development

et al. 2017

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Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues. Using Caki-1 cells as a model, we analyzed the role of MCPIP1 in cancer development. We showed that MCPIP1 expression depends on the proteasome activity; however, hypoxia and hypoxia inducible factor 2 alfa (HIF2α) are key factors lowering MCPIP1 expression. Furthermore, we found that MCPIP1 negatively regulates HIF1α and HIF2α levels and in the case of the last one, the mechanism is based on the regulation of the half time of transcript coding for HIF2α. Enhanced expression of MCPIP1 in Caki-1 cells results in a downregulation of transcripts encoding VEGFA, GLUT1, and IL-6. Furthermore, MCPIP1 decreases the activity of mTOR and protein kinase B (Akt) in normoxic conditions. Taken together, MCPIP1 contributes to the ccRCC development. Electronic supplementary materialThe online version of this article (doi:10.1007/s10456-017-9540-2) contains supplementary material, which is available to authorized users.

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“…There is a growing body of evidence showing that MCPIP1 also plays a critical role in cell differentiation. Although the exact mechanism of this process is not yet clear, the literature suggests MCPIP1 plays an important role in differentiation of neuronal progenitor cells, monocytes, and preadipocytes [11][12][13][14]. Differentiation of preadipocytes towards adipocytes, called adipogenesis, is an important process tightly controlled by communication between individual cells and with the extracellular environment.…”

Section: Introductionmentioning

confidence: 99%

Integrative genomics reveal a role for MCPIP1 in adipogenesis and adipocyte metabolism

Losko

Dolicka

Pydyn

et al. 2019

Cell. Mol. Life Sci.

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Obesity is considered a serious chronic disease, associated with an increased risk of developing cardiovascular diseases, non-alcoholic fatty liver disease and type 2 diabetes. Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1) is an RNase decreasing stability of transcripts coding for inflammation-related proteins. In addition, MCPIP1 plays an important role in the regulation of adipogenesis in vitro by reducing the expression of key transcription factors, including C/EBPβ. To elucidate the role of MCPIP1 in adipocyte biology, we performed RNA-Seq and proteome analysis in 3T3-L1 adipocytes overexpressing wild-type ( WT MCPIP1) and the mutant form of MCPIP1 protein ( D141N MCPIP1). Our RNA-Seq analysis followed by confirmatory Q-RT-PCR revealed that elevated MCPIP1 levels in 3T3-L1 adipocytes upregulated transcripts encoding proteins involved in signal transmission and cellular remodeling and downregulated transcripts of factors involved in metabolism. These data are consistent with our proteomic analysis, which showed that MCPIP1 expressing adipocytes exhibit upregulation of proteins involved in cellular organization and movement and decreased levels of proteins involved in lipid and carbohydrate metabolism. Moreover, MCPIP1 adipocytes are characterized by decreased level of insulin receptor, reduced insulin-induced Akt phosphorylation, as well as depleted Glut4 level and impaired glucose uptake. Overexpression of Glut4 in 3T3-L1 cells expressed WT MCPIP1 rescued adipogenesis. Interestingly, we found decreased level of MCPIP1 along with an increase in body mass index in subcutaneous adipose tissue. The presented data show a novel role of MCPIP1 in modulating insulin sensitivity in adipocytes. Overall, our findings demonstrate that MCPIP1 is an important regulator of adipogenesis and adipocyte metabolism.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Monocyte chemoattractant protein-induced protein 1 impairs adipogenesis in 3T3-L1 cells

Cited by 34 publications

References 25 publications

MCPIP1, alias Regnase-1 binds and cleaves mRNA of C/EBPβ

MCPIP1, alias Regnase-1 binds and cleaves mRNA of C/EBPβ

MCPIP1 contributes to clear cell renal cell carcinomas development

Integrative genomics reveal a role for MCPIP1 in adipogenesis and adipocyte metabolism

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