Early growth response genes 2 and 3 induced by AP-1 and NF-κB modulate TGF-β1 transcription in NK1.1− CD4+ NKG2D+ T cells

Han, Sen; Zhu, Tao; Ding, Shizhen; Wen, Jianqiang; Lin, Zhijie; Lu, Guotao; Xiao, Weiming; Ding, Yanbing; Jia, Xiao‐Bin; Chen, Huabiao; Gong, Weijuan

doi:10.1016/j.cellsig.2020.109800

Cited by 4 publications

(1 citation statement)

References 37 publications

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“…[ 55 ] Notably, a specific member of this family, EGR3, reportedly modulates TGF‐β1 transcription in T cells. [ 56 ] This member also exerts a profibrotic role in skin and cardiac fibroblasts by stimulating the expression of ACTA2 and COL1A1 genes. [ 25 , 57 ] Our RNA‐seq data revealed a significant upregulation of EGR3 in CA‐treated LX‐2 cells.…”

Section: Discussionmentioning

confidence: 99%

Loss of SLC27A5 Activates Hepatic Stellate Cells and Promotes Liver Fibrosis via Unconjugated Cholic Acid

Wu,

Liu,

Xia

et al. 2023

Advanced Science

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Although the dysregulation of bile acid (BA) composition has been associated with fibrosis progression, its precise roles in liver fibrosis is poorly understood. This study demonstrates that solute carrier family 27 member 5 (SLC27A5), an enzyme involved in BAs metabolism, is substantially downregulated in the liver tissues of patients with cirrhosis and fibrosis mouse models. The downregulation of SLC27A5 depends on RUNX family transcription factor 2 (RUNX2), which serves as a transcriptional repressor. The findings reveal that experimental SLC27A5 knockout (Slc27a5−/−) mice display spontaneous liver fibrosis after 24 months. The loss of SLC27A5 aggravates liver fibrosis induced by carbon tetrachloride (CCI4) and thioacetamide (TAA). Mechanistically, SLC27A5 deficiency results in the accumulation of unconjugated BA, particularly cholic acid (CA), in the liver. This accumulation leads to the activation of hepatic stellate cells (HSCs) by upregulated expression of early growth response protein 3 (EGR3). The re‐expression of hepatic SLC27A5 by an adeno‐associated virus or the reduction of CA levels in the liver using A4250, an apical sodium‐dependent bile acid transporter (ASBT) inhibitor, ameliorates liver fibrosis in Slc27a5−/− mice. In conclusion, SLC27A5 deficiency in mice drives hepatic fibrosis through CA‐induced activation of HSCs, highlighting its significant implications for liver fibrosis treatment.

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Section: Discussionmentioning

confidence: 99%

Loss of SLC27A5 Activates Hepatic Stellate Cells and Promotes Liver Fibrosis via Unconjugated Cholic Acid

Wu,

Liu,

Xia

et al. 2023

Advanced Science

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Vibration accelerates orthodontic tooth movement by inducing osteoclastogenesis via transforming growth factor-β signalling in osteocytes

Sasaki

Takeshita

Fukunaga

et al. 2022

European Journal of Orthodontics

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Summary Background We previously found the conditions of supplementary vibration that accelerated tooth movement and induced bone resorption in an experimental rat tooth movement model. However, the molecular biological mechanisms underlying supplementary vibration-induced orthodontic tooth movement are not fully understood. Transforming growth factor (TGF)-β upregulates osteoclastogenesis via induction of the receptor activator of nuclear factor kappa B ligand expression, thus TGF-β is considered an essential cytokine to induce bone resorption. Objectives The aim of this study is to examine the role of TGF-β during the acceleration of orthodontic tooth movement by supplementary vibration. Materials and methods In experimental tooth movement, 15 g of orthodontic force was loaded onto the maxillary right first molar for 28 days. Supplementary vibration (3 g, 70 Hz) was applied to the maxillary first molar for 3 min on days 0, 7, 14, and 21. TGF-β receptor inhibitor SB431542 was injected into the submucosal palatal and buccal areas of the maxillary first molars once every other day. The co-culture of RAW264.7 cells and MLO-Y4 cells was used as an in vitro osteoclastogenesis model. Results SB431542 suppressed the acceleration of tooth movement and the increase in the number of osteoclasts by supplementary vibration in our experimental rat tooth movement model. Immunohistochemical analysis showed supplementary vibration increased the number of TGF-β1-positive osteocytes in the alveolar bone on the compression side during the experimental tooth movement. Moreover, vibration-upregulated TGF-β1 in MLO-Y4 cells induced osteoclastogenesis. Conclusions Orthodontic tooth movement was accelerated by supplementary vibration through the promotion of the production of TGF-β1 in osteocytes and subsequent osteoclastogenesis.

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Single-cell sequencing provides insights into the landscape of ovary in PCOS and alterations induced by CUMS

Zuo

Liu

Chen

et al. 2023

American Journal of Physiology-Endocrinology and Metabolism

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Introduction: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder related to psychological distress. However, the mechanism underlying increased prevalence of depression in PCOS remained unclear. This study aimed to explore the unique transcriptional landscape of ovary and offered a platform to explore the mechanism of PCOS, as well as the influences caused by depression. Methods: The PCOS rat model was established by letrozole while PCOS rat model with depression was established by letrozole combined with chronic unpredicted mild stress (CUMS). Then single-cell RNA sequencing (scRNA-Seq) was applied to analyze the transcriptional features of rat ovaries. Results: Granulosa cells (GCs) and fibroblasts (Fibros) accounted for the top 2 clusters of total 12 cell types. There were 9 clusters in GCs, related to inflammatory response, endoplasmic reticulum (ER) stress and steroidogenesis. The expression of DEG Hes1 was higher in PCOS and PCOS+CUMS group, exhibiting enhanced expression by pseudotime and positively related to inflammation. Pseudotemporal analysis revealed that inflammation contributed to the different GCs distributions. Moreover, analysis of DEGs and GO function enrichment revealed CUMS aggravated inflammation in PCOS GCs possibly via interferon signaling pathway. In theca cells (TCs), 9 clusters were observed and some of them were relevant to inflammation, ER stress and lipid metabolism. DEGs Ass1, Insl3, Ifi27 were positively related to Cyp17a1, and Ces1d might contribute to the different trajectory of TCs. Subsequent scRNA-seq revealed signature profile of endothelial cells (ECs) and Fibros, which suggest that inflammation induced damage of ECs and Fibro, further exacerbated by CUMS. Finally, analysis of T cells and mononuclear phagoytes (MPs) revealed the existence of immune dysfunction, among which interferon signaling played a critical role. Conclusions: These findings provided more acknowledge for better understanding PCOS from the view of inflammation and identified new biomarkers and targets for the treatment of PCOS with psychological diseases.

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Early growth response genes 2 and 3 induced by AP-1 and NF-κB modulate TGF-β1 transcription in NK1.1− CD4+ NKG2D+ T cells

Cited by 4 publications

References 37 publications

Loss of SLC27A5 Activates Hepatic Stellate Cells and Promotes Liver Fibrosis via Unconjugated Cholic Acid

Loss of SLC27A5 Activates Hepatic Stellate Cells and Promotes Liver Fibrosis via Unconjugated Cholic Acid

Vibration accelerates orthodontic tooth movement by inducing osteoclastogenesis via transforming growth factor-β signalling in osteocytes

Single-cell sequencing provides insights into the landscape of ovary in PCOS and alterations induced by CUMS

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