Celastrol targets LRP1 to inhibit fibroblast-macrophage crosstalk and ameliorates psoriasis progression
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PROVIDER: PRJNA967368 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: This study aimed to explore the mechanism of Celastrol in improving psoriasis through single-cell transcriptomics Methods: Supplementation with intragastric administration of celastrol in C57BL/6 mice to observe its effect on IMQ-induced psoriasis. Single-cell RNA sequencing were performed to explore the role of celastrol for IMQ-induced psoriasis. Results: A natural product library was used to screen for a small molecule compound, celastrol, that could interfere with fibroblast-macrophage communication. It was demonstrated that celastrol targeted low-denisity lipoprotein receptor-related protein 1 (LRP1) to inhibit fibroblast secretion of CCL2 and inhibited psoriasis progression by reducing its recruitment to macrophages, thereby blocking communication between the two cells Conclusion: We report that celastrol targeted low-denisity lipoprotein receptor-related protein 1 (LRP1) to inhibit fibroblast secretion of CCL2 and inhibited psoriasis progression by reducing its recruitment to macrophages. The use of celastrol maybe a noveltherapeuticoption for psoriasis.
2024-04-20 | GSE231728 | GEO
Project description:In the present study, we analyzed single-cell multi-omics data from psoriasis patients and healthy individuals and found that more fibroblast-macrophage communication was present in the dermis of psoriasis lesions, exacerbating psoriasis progression. A natural product library was used to screen for a small molecule compound, celastrol, that could interfere with fibroblast-macrophage communication. It was demonstrated that celastrol targeted low-denisity lipoprotein receptor-related protein 1 (LRP1) to inhibit fibroblast secretion of CCL2 and inhibited psoriasis progression by reducing its recruitment to macrophages, thereby blocking communication between the two cells. Moreover, conditional knockdown of LRP1 by fibroblasts significantly improved psoriasis in mice, suggesting that LRP1 may be an important target for the treatment of psoriasis.
2024-03-31 | GSE230842 | GEO
Project description:Celastrol targets LRP1 to inhibit fibroblast-macrophage crosstalk and ameliorates psoriasis progression
| PRJNA962821 | ENA
Project description:Purpose: The goals of this study was to (1) evaluate the protective effect of celastrol on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis and (2) which genes were recovered by celastrol. Methods:To investigate the protective effect of celastrol on ANIT-induced cholestasis, the WT mice were randomly assigned into two groups, respectively (n=3): (1) ANIT; (2) ANIT+Celastrol. ANIT+Celastrol group was orally treated with celastrol (10 mg/kg dissolved in 1% DMSO + 2% Tween 80 + 97% water) for 5 consecutive days. After celastrol was treated for 3 days, ANIT and ANIT+Celastrol groups were given a single oral dose of ANIT. All mice were killed 48 h after ANIT administration. Liver samples were harvested and frozen at -80 °C before analysis. Results: A total of 978 DEGs were identified. Large numbers of these DEGs were related to activation of SIRT1, which included increased FXR signaling and inhibition of PPARγ, nuclear factor-kappa B (NF-κB), and P53 signaling. Conclusions: Celastrol could protect ANIT-induced cholestasis by recovering disrupted Sirt1 level.
2018-02-09 | GSE110391 | GEO
Project description:Celastrol is a natural product that affects LNCaP gene expression by 6h; We used microarrays to detail the global programme of gene expression affected by celastrol treatment at 6h Experiment Overall Design: LNCaP cells were grown to 50% confluency and treated with celastrol for 6h prior to direct Trizol lysis and RNA isolation
2008-11-07 | E-GEOD-5505 | biostudies-arrayexpress
Project description:Celastrol has been shown to sensitize leptin receptor signaling and reduce ER stress. Current microarray data provide the gene expression profile in mouse embryonic fibroblasts (MEFs) after Celastrol treatment compared with control.
2016-07-08 | GSE84154 | GEO
Project description:Given that celastrol?s leptin-sensitizing effect requires high levels of circulating leptin, but lean mice have low levels of circulating leptin so that celastrol has no effect on lean mice. Analysis celastrol-induced hypothalamic gene expression profile change in lean mice will also be serving as negative control for DIO mice analysis.
2018-12-27 | GSE124356 | GEO
Project description:The polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease of both localized and systemic low-grade inflammation. The Sirtuin1 enzyme thought to mediate the effects of resveratrol is present in skin and resveratrol is known to downregulate NF-κB; a major contributor in the development of psoriasis. Consequently we investigated whether resveratrol has an effect on an Imiquimod induced psoriasis-like skin inflammation in mice and sought to identify candidate genes, pathways and interleukins mediating the observed effects. The study consisted of three treatment groups: A control group, an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was assessed using elements of the Psoriasis Area Severity Index, actual skin thickness measurements, and histological examination. We performed an RNA microarray from lesional skin and afterwards Ingenuity pathway analysis to identify affected signalling pathways. Our microarray was compared to a previously deposited microarray to determine if gene changes were psoriasis-like, and to a human microarray to determine if findings could be relevant in a human setting. Imiquimod treatment induced a psoriasis-like skin inflammation. Resveratrol significantly diminished the severity of the psoriasis-like skin inflammation. The RNA microarray revealed a psoriasis-like gene expression-profile in the Imiquimod treated group, and highlighted several resveratrol dependent changes in relevant genes, such as increased expression of genes associated with retinoic acid stimulation and reduced expression of genes involved in IL-17 dependent pathways (e.g.IL-17A, IL-17F,IL-23p19 ). Quantitative PCR confirmed a resveratrol dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing psoriasis. In conclusion, resveratrol ameliorates psoriasis, and changes in expression of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19 mRNA levels in a beneficial manner suggests it might have a role in the treatment of psoriasis and should be explored further in a human setting.
2015-11-17 | GSE63684 | GEO
Project description:Stress response pathways allow cells to rapidly sense and respond to deleterious environmental changes, including those caused by pathophysiological disease states. A previous screen for small molecules capable of activating the human heat shock response identified the triterpenoid celastrol as a potent activator of the heat shock transcription factor HSF1. We show here that celastrol likewise activates the homologous Hsf1 of Saccharomyces cerevisiae. Celastrol induced Hsf1 hyperphosphorylation and concurrently activated a synthetic transcriptional reporter as well as endogenous inducible Hsp70 proteins at the same effective concentration seen in mammalian cells. Moreover, celastrol treatment conferred significant resistance to subsequent lethal heat shock. Transcriptional profiling experiments revealed that in addition to Hsf1, celastrol treatment induced the Yap1-dependent oxidant defense regulon. Oxidative stress-responsive genes were likewise induced in mammalian cells, demonstrating that celastrol simultaneously activates two major cellular stress-mediating pathways. As the induction of cellular stress pathways has implications in the treatment of a variety of human diseases including neurodegenerative diosorders, cardiovascular disease and cancer, celastrol thus represents an attractive therapeutic compound. Keywords: single-dose, single time-point gene induction by natural small molecule celastrol compared to heat shock in wild type (BY4741) Saccahromyces cerevisiae
2006-08-26 | GSE5608 | GEO
Project description:Celastrol is a natural product that affects LNCaP gene expression by 6h We used microarrays to detail the global programme of gene expression affected by celastrol treatment at 6h Keywords: drug treatment
2006-09-01 | GSE5505 | GEO