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Pretreatment of aged mice with retinoic acid restores alveolar regeneration via upregulation of reciprocal PDGFRA signaling

ABSTRACT: Reciprocal PDGFA signaling activates regenerative fibroblasts that support alveolar epithelial cell differentiation and repair, providing a potential therapeutic strategy to influence the pathogenesis of IPF.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE157440 | GEO | 2021/01/05

REPOSITORIES: GEO

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Pretreatment of aged mice with retinoic acid restores alveolar regeneration via upregulation of reciprocal PDGFRA signaling

Project description:Pretreatment of aged mice with retinoic acid restores alveolar regeneration via upregulation of reciprocal PDGFRA signaling

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Upregulation of SOX9 inhibits the growth of human and mouse melanomas and restores their sensitivity to retinoic acid.

Project description:Treatments for primary and metastatic melanomas are rarely effective. Even therapeutics such as retinoic acid (RA) that are successfully used to treat several other forms of cancer are ineffective. Recent evidence indicates that the antiproliferative effects of RA are mediated by the transcription factor SOX9 in human cancer cell lines. As we have previously shown that SOX9 is expressed in normal melanocytes, here we investigated SOX9 expression and function in human melanomas. Although SOX9 was expressed in normal human skin, it was increasingly downregulated as melanocytes progressed to the premalignant and then the malignant and metastatic states. Overexpression of SOX9 in both human and mouse melanoma cell lines induced cell cycle arrest by increasing p21 transcription and restored sensitivity to RA by downregulating expression of PRAME, a melanoma antigen. Furthermore, SOX9 overexpression in melanoma cell lines inhibited tumorigenicity both in mice and in a human ex vivo model of melanoma. Treatment of melanoma cell lines with PGD2 increased SOX9 expression and restored sensitivity to RA. Thus, combined treatment with PGD2 and RA substantially decreased tumor growth in human ex vivo and mouse in vivo models of melanoma. The results of our experiments targeting SOX9 provide insight into the pathophysiology of melanoma. Further, the effects of SOX9 on melanoma cell proliferation and RA sensitivity suggest the encouraging possibility of a noncytotoxic approach to the treatment of melanoma.

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Gene expression of Col, Van and reciprocal hybrids

Project description:Gene expression of Col, Van and reciprocal hybrids using double-stranded cDNA followed by bioprime random labeling, and hybridization to AtTILE1 forward array. Study on gene expression polymorphism between arabidopsis thaliana accessions Col-0 and Van-0. Study on the inheritance of gene expression in reciprocal hybrids. Keywords: cDNA hybridization

2008-04-11 | GSE8891 | GEO

Oncogene-dependent regulation of tumor cells via stromal reciprocal signalling

Project description:Cancer is a heterocellular disease composed of tumor cells and stromal cells. Although stromal cells are known to regulate cancer progression, oncogene-dependent signalling through heterocellular cancer systems remains poorly elucidated. Here, we describe KRASG12D-dependent ‘reciprocal’ signalling across tumor and stromal Pancreatic Ductal Adenocarcinoma (PDA) cells. Heterocellular multivariate phosphoproteomics demonstrates how an oncogenic cue (KRASG12D), a trans-cellular signal (SHH), and stromal cells drive a reciprocal response in tumor cells. KRASG12D-dependent reciprocal signalling regulates the tumor cell phosphoproteome, total proteome, and mitochondria activity via an IGFR1/AXL-AKT axis. The reciprocal KRASG12D signalling state requires a heterocellular context and is unreachable by cell-autonomous oncogenic KRAS alone. These findings provide evidence that oncogenic KRAS regulates tumor cells via heterocellular reciprocation.

2015-06-27 | GSE70351 | GEO

Resveratrol Pretreatment Ameliorates Concanavalin A-Induced Advanced Renal Glomerulosclerosis in Aged Mice through Upregulation of Sirtuin 1-Mediated Klotho Expression.

Project description:Aging kidneys are characterized by an increased vulnerability to glomerulosclerosis and a measurable decline in renal function. Evidence suggests that renal and systemic klotho and sirtuin 1 (SIRT1) deficiencies worsen kidney damage induced by exogenous stresses. The aim of this study was to explore whether resveratrol would attenuate concanavalin A (Con A)-induced renal oxidative stress and advanced glomerulosclerosis in aged mice. Aged male C57BL/6 mice were treated orally with resveratrol (30 mg/kg) seven times (12 h intervals) prior to the administration of a single tail-vein injection of Con A (20 mg/kg). The plasma and urinary levels of kidney damage markers were evaluated. The kidney histopathology, renal parameters, and oxidative stress levels were measured. Furthermore, klotho was downregulated in mouse kidney mesangial cells that were pretreated with 25 µM resveratrol followed by 20 µg/mL Con A. The urinary albumin/creatinine ratio, blood urea nitrogen, kidney mesangial matrix expansion, tubulointerstitial fibrosis, and renal levels of ?-smooth muscle actin, transforming growth factor beta, fibronectin, procollagen III propeptide, and collagen type I significantly increased in Con A-treated aged mice. Aged mice kidneys also showed markedly increased levels of 8-hydroxydeoxyguanosine (8-OH-dG) and reactive oxygen species (ROS), with reduced superoxide dismutase activity and levels of glutathione, klotho, and SIRT1 after Con A challenge. Furthermore, in kidney mesangial cells, klotho silencing abolished the effects of resveratrol on the Con A-mediated elevation of the indices of oxidative stress and the expression of glomerulosclerosis-related factors. These findings suggest that resveratrol protects against Con A-induced advanced glomerulosclerosis in aged mice, ameliorating renal oxidative stress via the SIRT1-mediated klotho expression.

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Oncogene-dependent regulation of tumor cells via stromal reciprocal signalling

2015-06-27 | E-GEOD-70351 | biostudies-arrayexpress

Transcriptomic profile of two tomato cultivars and their reciprocal hybrids

Project description:The tomato cultivars Querubín FCA (Q) and Gema FCA (G) as parental genotypes and the hybrids Q x G and G x Q were selected to perform and investigation of the gene actions involved in gene expression profile. In this work, we aimed to study the differences between parental lines and the presence of heterosis and reciprocal effects in the reciprocal hybrids.

2022-12-31 | GSE199011 | GEO

16p11.2 Reciprocal Genomic Disorder Tissue-Specific Mouse Molecular Signatures

Project description:Transcriptome analyses of 16p11.2 reciprocal genomic disorder (RGD) deletion and wild type mouse across cortex, striatum and cerebellum tissues.

2019-03-30 | GSE126559 | GEO

Genome-wide profiling of DNA methylation in two Arabidopsis ecotypes and their reciprocal hybrids

Project description:This SuperSeries is composed of the following subset Series: GSE34655: Genome-wide profiling of DNA methylation in two Arabidopsis ecotypes and their reciprocal hybrids - mRNA-seq GSE34656: Genome-wide profiling of DNA methylation in two Arabidopsis ecotypes and their reciprocal hybrids - small RNA-seq GSE34657: Genome-wide profiling of DNA methylation in two Arabidopsis ecotypes and their reciprocal hybrids - Bisulfite-seq Refer to individual Series

2011-12-22 | E-GEOD-34658 | biostudies-arrayexpress

CG Methylation of Col, Van and reciprocal hybrids using HpaII and MspI digestion

Project description:CG Methylation of Col, Van and reciprocal hybrids using HpaII and MspI digestion followed by bioprime random labeling, and hybridization to AtTILE1 forward array. Study on constitutive and ploymorphic CG methylation between arabidopsis thaliana accessions Col-0 and Van-0. Study on the inheritance of CG methylation in reciprocal hybrids. Keywords: genomic hybridization

2008-04-11 | GSE8890 | GEO

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