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Indian Hedgehog release from inflamed epithelia links TNF-alpha to organ fibrosis

ABSTRACT: Indian Hedgehog release from inflamed epithelia links TNF-alpha to organ fibrosis

PROVIDER: PRJNA737404 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14804522_1.fastq.gz	Fastqsanger.gz
	SRR14804522_2.fastq.gz	Fastqsanger.gz
	SRR14804523_1.fastq.gz	Fastqsanger.gz
	SRR14804523_2.fastq.gz	Fastqsanger.gz
	SRR14804524_1.fastq.gz	Fastqsanger.gz

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Indian Hedgehog release from inflamed epithelia links TNF-alpha to organ fibrosis

Project description:In chronic kidney disease (CKD) and with ageing, individuals lose regenerative capacity after renal injury and are predisposed to progressive fibrosis and cardiovascular disease. With ageing and CKD increased numbers of activated leukocytes are present in the circulation and within the kidney where they correlate with progressive fibrosis. The potential role of activated leukocytes in mediating progressive renal and systemic fibrosis remains incompletely understood. Here, we show that tumour necrosis factor alpha (TNFa) released with injury and aging promotes renal and cardiac fibrosis. We identify a Ubiquitin D expressing population of TNFa induced inflammatory proximal tubular epithelia (iPT) responsible for Indian Hedgehog release in aged and fibrotic kidneys. Indian Hedgehog production by iPT cells activates canonical Hedgehog signalling in Gli1+ stromal cells leading to activation, proliferation and fibrosis deposition. Our data links the immune activation seen in aging and chronic kidney disease to cardio-renal fibrosis. This provides multiple targets for antifibrotic therapies which we validate in murine models of aging and kidney disease.

2023-01-30 | GSE178109 | GEO

The function of morphogen Indian Hedgehog in the colon

Project description:The morphogen Indian Hedgehog plays a very important role during intestinal embryogenesis, but also maintains homeostasis of the adult gut. Intestinal Indian Hedgehog is expressed by the intestinal epithelium and signals in paracrine manner to fibroblasts in the stromal compartment. Unresolved deletion of Ihh from the intestinal epithelium leads to a severe enterocolitis. We studied the short term changes in the colon upon deletion of Ihh from the epithelial layer.

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Transcription profiling of mouse E18.5 intestinal mesenchyme treated with Sonic or Indian hedgehog ligand to identify targets regulated by Hedgehog signaling

Project description:Epithelial Hedgehog (Hh) ligands regulate several aspects of fetal intestinal organogenesis and emerging data implicate the Hh pathway in inflammatory signaling in adult colon. We investigated the effects of chronic Hh inhibition in vivo and profiled molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme. Experiment Overall Design: E18.5 intestinal mesenchyme was isolated and cultured. Mesenchyme was treated with Sonic (Shh) or Indian (Ihh) hedgehog ligand or Vehicle (control) acutely to identify targets regulated by Hh signaling in intestinal mesenchyme.

2009-11-10 | E-GEOD-17840 | biostudies-arrayexpress

Gene expression profiling of conditional ablation of Indian hedgehog in the mouse uterus

Project description:Conditional ablation of Indian hedgehog (Ihh) in the murine uterus results in mice that are sterile due to defects in embryo implantation. We performed microarray analysis on these mice at the time point at which the Ihh target genes are induced by the administration of exogenous hormone to mimic day 3.5 of pregnancy. This analysis identified 863 genes altered by the conditional ablation of Ihh. Of these, genes that regulated the cell cycle were overrepresented. In addition, genes involved in epidermal growth factor (EGF) and estrogen (E2) signaling were found to be deregulated upon Ihh ablation. Furthermore, upon conditional ablation of Ihh, 15 month old mice exhibited hallmarks of estrogenized uteri such as cystically dilated glands and hyalinized stroma. Thus, Ihh regulates embryo implantation by impacting the cell cycle, EGF signaling, and E2 signaling. Keywords: two group comparison We conditionally ablated Indian hedgehog in the mouse uterus using the PRcre mouse model (PRcre/+Ihhf/f; Ihhd/d). High density DNA microarray analysis was performed on Day -1 of the artificial decidual response on Ihhf/f and Ihhd/d uteri.

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A multipartite enhancer ensemble coordinates pleiotropic developmental functions of Indian hedgehog

Project description:Copy number variations (CNVs) including enhancers frequently appear associated with disease, induced by pathomechanisms that are poorly understood. Here we show through transgenic reporter and genome editing studies in mice that Indian hedgehog (Ihh) is regulated by a constellation of enhancers of unusual complexity and we uncover how duplications within this enhancer architecture cause phenotypes reminiscent of those observed in human patients. At least nine enhancers with distinct combinations of activities orchestrate the expression of Ihh in the digit anlagen, growth plates, skull sutures, and digit tips. Consecutive deletions show that they function in an additive manner resulting in growth defects. Duplications, in contrast, cause not only dose-dependent upregulation of Ihh, but also misexpression, leading to phenotypes influenced by the copy number and relative positioning of individual elements. Taken together, our results uncover a complex regulatory landscape at the Ihh locus and exemplify the intricate and precise control of gene expression during morphogenetic processes.

2017-07-04 | GSE95062 | GEO

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Indian Hedgehog suppresses a stromal cell driven intestinal immune response

Project description:Indian Hedgehog suppresses a stromal cell driven intestinal immune response

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Gene expression profiling of conditional ablation of Indian hedgehog in the mouse uterus

2010-03-01 | GSE19517 | GEO

RNA-seq for inflamed and non-inflamed mucosa in patients with Crohn's disease

Project description:RNA-seq for inflamed and non-inflamed mucosa in patients with Crohn's disease

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