The nuclear receptor subfamily 4 group A1 in human disease

Wang, Hongshuang; Zhang, Mengjuan; Fang, Fang; Xu, Chang; Liu, Jiazhi; Gao, Lanjun; Zhao, Chenchen; Wang, Zheng; Zhong, Yan; Wang, Xiangting

doi:10.1139/bcb-2022-0331

Cited by 4 publications

(4 citation statements)

References 143 publications

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“…The BMP family has also been well-described to exhibit anti-fibrotic effects (De Langhe et al, 2015;Guan et al, 2022;Pegorier et al, 2010;Tan et al, 2019). The anti-fibrotic effects of the nuclear receptor family and aldehyde dehydrogenase (ALDH) gene superfamily have been shown in our previous work (Tan et al, 2021) and by others (Ma et al, 2018;Takahashi et al, 2021;Wang et al, 2023). Pentraxin 3 (Ptx3) has been shown to protect against BLM-induced lung fibrosis in mice as well (Maccarinelli et al, 2021).…”

Section: Discussionmentioning

confidence: 86%

“…Five hundred and ten of 595 genes (85.7%) that significantly increase during both processes increase more following BLM, whereas 200 of 267 (74.9%) common decreased genes decrease more following BLM. Furthermore, we identified several genes previously documented to moderate pro‐fibrotic responses uniquely upregulated after PNX but not BLM (Figure 3f), including Ptgs2 , responsible for synthesis of the antifibrotic prostaglandin E2 (Bauman et al., 2010; Huang et al., 2007; Keerthisingam et al., 2001; Lama et al., 2002), Bone Morphogenetic Protein (BMP) ligands ( Bmp2 , Bmp7 ) (De Langhe et al., 2015; Guan et al., 2022; Pegorier et al., 2010; Tan et al., 2019), the Nuclear Receptor 4A (NR4A) Family ( Nr4a1 , Nr4a2 , Nr4a3 ), and the aldehyde dehydrogenase (ALDH) gene superfamily ( Aldh1a1 ) (Ma et al., 2018; Takahashi et al., 2021; Wang et al., 2023). These previously described anti‐fibrotic transcripts elevated after PNX but not BLM might contribute to the lower magnitude of fibrotic responses in PNX compared with BLM (Figure 3e).…”

Section: Resultsmentioning

confidence: 99%

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RNA‐sequencing reveals differential fibroblast responses to bleomycin and pneumonectomy

Wellmerling,

Dresler,

Meridew

et al. 2024

Physiological Reports

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Pulmonary fibrosis is characterized by pathological accumulation of scar tissue in the lung parenchyma. Many of the processes that are implicated in fibrosis, including increased extracellular matrix synthesis, also occur following pneumonectomy (PNX), but PNX instead results in regenerative compensatory growth of the lung. As fibroblasts are the major cell type responsible for extracellular matrix production, we hypothesized that comparing fibroblast responses to PNX and bleomycin (BLM) would unveil key differences in the role they play during regenerative versus fibrotic lung responses. RNA‐sequencing was performed on flow‐sorted fibroblasts freshly isolated from mouse lungs 14 days after BLM, PNX, or sham controls. RNA‐sequencing analysis revealed highly similar biological processes to be involved in fibroblast responses to both BLM and PNX, including TGF‐β1 and TNF‐α. Interestingly, we observed smaller changes in gene expression after PNX than BLM at Day 14, suggesting that the fibroblast response to PNX may be muted by expression of transcripts that moderate pro‐fibrotic pathways. Itpkc, encoding inositol triphosphate kinase C, was a gene uniquely up‐regulated by PNX and not BLM. ITPKC overexpression in lung fibroblasts antagonized the pro‐fibrotic effect of TGF‐β1. RNA‐sequencing analysis has identified considerable overlap in transcriptional changes between fibroblasts following PNX and those overexpressing ITPKC.

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Section: Discussionmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

RNA‐sequencing reveals differential fibroblast responses to bleomycin and pneumonectomy

Wellmerling,

Dresler,

Meridew

et al. 2024

Physiological Reports

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show abstract

“…Nr4a1 is an activity‐dependent transcription factor rapidly transcribed in response to neuronal activity and stress 46 . Nr4a1 , a key mediator during the regulation of inflammatory disease factors, 47 could inactivate the MAPK/ERK/CREB signaling pathway 48 . Up‐regulation of Nr4a1 expression may inhibit oxidative stress induced volatile antidepressant effects 49 .…”

Section: Discussionmentioning

confidence: 99%

“… 46 Nr4a1 , a key mediator during the regulation of inflammatory disease factors, 47 could inactivate the MAPK/ERK/CREB signaling pathway. 48 Up‐regulation of Nr4a1 expression may inhibit oxidative stress induced volatile antidepressant effects. 49 According to clinical studies, the expression level of inflammatory factor Nr4a1 was significantly downregulated in the transcriptome sequencing of the dentate gyrus in the MDD patients compared with the control, suggesting that neuroinflammation plays a crucial role in MDD.…”

Section: Discussionmentioning

confidence: 99%

Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota–gut–brain axis in corticosterone combined with chronic restraint stress‐induced mice

Tian,

Wang,

Teng

et al. 2023

CNS Neurosci Ther

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BackgroundThe microbiota–gut–brain axis plays a critical role in neuropsychiatric disorders, particularly anxious depression, and attracts more attention gradually. Zhi Zi Chi decoction (ZZCD) consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a classic formula in clinic and widely applied in anxiety and depression treatment. However, the underlying mechanisms of regulating microbiota–gut–brain axis in the treatment of anxious depression by oral administration of ZZCD remain elusive.Materials and MethodsIn this project, we clarified the origin and preparation methods of the Gardenia jasminoides J. Ellis and Glycine max (L.) Merr and examined the chemical ingredients of ZZCD by liquid chromatograph mass spectrometer. Then, corticosterone combined with chronic restraint stress was applied to establish an anxious depression model. After treated with ZZCD standard decoction, based on enzyme‐linked immunosorbent assay (ELISA), 16S rRNA technology, high‐throughput sequencing, quantitative RT‐PCR and fecal microbiota transplantation (FMT), the multiple associations between nucleus accumbens and intestinal flora in anxious depression mice were determined to clarify the mechanism of ZZCD in the treatment of anxiety and depression disorder.ResultsWe found various substances with antidepressant and antianxiety properties in ZZCD such as rosiridin and oleanolic acid. ZZCD could alleviate depressive and anxiety behaviors in anxious depression mice via regulating the disturbance of gut microbiota. Meanwhile, the bioactive compounds of ZZCD might directly active on neurodevelopment and neuroimmune‐related genes. Furthermore, the secretion of prolactin and estrogen, and interfering with mitogen‐activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were mainly involved in the multi‐target therapeutic effects of ZZCD against anxiety and depression.ConclusionsThese findings suggested that ZZCD exerts antidepressant effects pleiotropically through modulating the microbiota‐gut‐brain.

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Developing novel therapy for drug-induced gingival overgrowth by targeting NR4A1

Matsuda,

Mizuno

2023

Journal of the Japanese Society of Periodontology

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The nuclear receptor subfamily 4 group A1 in human disease

Cited by 4 publications

References 143 publications

RNA‐sequencing reveals differential fibroblast responses to bleomycin and pneumonectomy

RNA‐sequencing reveals differential fibroblast responses to bleomycin and pneumonectomy

Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota–gut–brain axis in corticosterone combined with chronic restraint stress‐induced mice

Developing novel therapy for drug-induced gingival overgrowth by targeting NR4A1

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