RARγ-C-Fos-PPARγ2 signaling rather than ROS generation is critical for all-trans retinoic acid-inhibited adipocyte differentiation

Wang, Xin; Yang, Peng; Liu, Jiangzheng; Wu, Hao; Yu, Weihua; Zhang, Tao; Han, Fangfang; Liu, Ying; Hai, Chen

doi:10.1016/j.biochi.2014.08.009

Cited by 26 publications

(23 citation statements)

References 59 publications

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“…ROS was detected by specific probe DHE as we previously described. 44,45 Briefly, the cells in specific dishes were stained with 10 μM DHE in serum-free DMEM medium (kept in the dark, 37°C) for 20 min. After washing twice with PBS, the cells were observed under a laser scanning confocal microscope (Olympus, FV10i).…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Wang

et al. 2017

Cell Death Differ

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Hepatocyte nuclear factor 1b (HNF1b) is a transcription factor belonging to the HNF family. We aimed to investigate the role of HNF1b in white adipocyte differentiation. The expression of HNF1b was reduced in white adipose tissue (WAT) of both diet-induced and genetic obese mice and decreased during the process of 3T3-L1 adipocyte differentiation. Downregulation of HNF1b enhanced 3T3-L1 adipocyte differentiation and upregulation of HNF1b inhibited this process. Upregulation of HNF1b inhibited peroxisome proliferator-activated receptor γ (PPARγ) and its target gene expression, while downregulation of HNF1b increased those genes expression. Overexpression of PPARγ suppressed HNF1b upregulation-induced inhibition of adipocyte differentiation. HNF1b can directly bind with the promoter of PPARγ in 3T3-L1 cells, which was decreased after adipogenic differentiation. HNF1b promoted apoptotic and autophagic cell death in early differentiated adipocytes through regulation of cell cycle progress and cell death-related factors, and thus inhibited the process of mitotic clonal expansion (MCE). HNF1b acted as an antioxidant regulator through regulating various antioxidant enzymes via binding with antioxidant response element. Oxidant treatment suppressed HNF1b upregulation-induced inhibition of adipocyte differentiation. Overall, our results suggest that HNF1b is a novel negative regulator of adipocyte differentiation through regulation of PPARγ signaling, MCE and redox state.

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Section: Discussionmentioning

confidence: 99%

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Wang

et al. 2017

Cell Death Differ

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“…Wang and cols. found that mouse adipocytes treated with all-trans-retinoic acid (ATRA) had higher RAR expression, RARg more so than RARα, with consequent decrease of PPARg expression (14). It is known that PPARg plays a role in GO development, and recently, we reported that OF from a GO patient treated with small doses of corticosteroid had higher PPARg gene expression.…”

Section: Discussionmentioning

confidence: 96%

“…The OF of GO patients express RA receptors, including RARα, and retinoids could inhibit adipocyte growth and differentiation, and induce apoptosis in these cells, consequently presenting therapeutic potential in GO (13,14). However, the development of severe GO has been associated with the simultaneous use of RA, recombinant thyroidstimulating hormone (TSH), and radioactive iodine (15).…”

Section: Introductionmentioning

confidence: 99%

Graves’ ophthalmopathy: low-dose dexamethasone reduces retinoic acid receptor-alpha gene expression in orbital fibroblasts

Cury¹,

Oliveira²,

Síbio³

et al. 2018

Archives of Endocrinology and Metabolism

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“…Retinoic acid (RA) is a key regulator of cell differentiation in many contexts [50][51][52], functioning so as to control gene expression via activation of the RA receptor (RAR) and retinoid X receptor (RXR) families of nuclear hormone receptors [53]. RARγ activation has been shown to be important for inhibiting PPARγ2 expression in 3T3-L1 adipocyte differentiation [54]. This thus suggests that RARγ may be an important regulator of adipogenesis.…”

Section: Discussionmentioning

confidence: 99%

A novel tsRNA-16902 regulating the adipogenicdifferentiation of human bone marrow mesenchymal stem cells

Wang

Mei

et al. 2020

Preprint

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Background: Transfer RNA-derived small RNAs (tsRNAs) are a recently discovered form of non-coding RNA capable of regulating myriad physiological processes. The role of tsRNAs in hMSC adipogenic differentiation, however, remains incompletely understood. The purpose of this study was to identify the novel tsRNA-16902 as a regulator of hMSC adipogenic differentiation.Methods: In this study we conducted transcriptomic sequencing of hMSCs after inducing their adipogenic differentiation, and we were thereby able to clarify the molecular mechanism underlying the role of tsRNA-16902 in this context via a series of molecular biology methods. Results: When we knocked down tsRNA-16902 expression, this impaired hMSC adipogenic differentiation and associated marker gene expression. Bioinformatics analyses further revealed tsRNA-16902 to target retinoic acid receptor γ (RARγ). Luciferase reporter assays also confirmed the ability of tsRNA-16902 to bind to the RARγ 3’-untranslated region. Consistent with this, RARγ overexpression led to impaired hMSC adipogenesis. Further analyses additionally revealed that Smad2/3 phosphorylation as increased in cells that either overexpressed RARγ or in which tsRNA-16902 had been knocked down. We also assessed the adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down and at the same time a Smad2/3 inhibitor was added to disrupt Smad2/3 phosphorylation. The adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down was further enhanced upon the addition of a Smad2/3 signaling inhibitor relative to tsRNA-16902 knockdown alone.Conclusions: Through a comprehensive profiling analysis of tsRNAs that were differentially expressed in the context of hMSC adipogenic differentiation, we were able to identify tsRNA-16902 as a previously uncharacterized regulator of adipogenesis. tsRNA-16902 is able to regulate hMSC adipogenic differentiation by targeting RARγ via the Smad2/3 signaling pathway. Together our results may thus highlight novel strategies of value for treating obesity.

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RARγ-C-Fos-PPARγ2 signaling rather than ROS generation is critical for all-trans retinoic acid-inhibited adipocyte differentiation

Cited by 26 publications

References 59 publications

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation

Graves’ ophthalmopathy: low-dose dexamethasone reduces retinoic acid receptor-alpha gene expression in orbital fibroblasts

A novel tsRNA-16902 regulating the adipogenicdifferentiation of human bone marrow mesenchymal stem cells

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