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The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche

ABSTRACT: The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche

PROVIDER: PRJNA607990 | ENA |

REPOSITORIES: ENA

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The secreted protease Adamts18 links mammary epithelial hormone action to extracellular matrix changes and stem cell niche function

Project description:The secreted protease Adamts18 links mammary epithelial hormone action to extracellular matrix changes and stem cell niche function

| PRJNA607942 | ENA

The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche

Project description:Estrogens and progesterone control mammary gland development and breast carcinogenesis via their cognate receptors expressed in a subset of cells of the luminal layer of the mammary epithelium. The extracellular matrix (ECM) including the basement membrane (BM) is important in breast physiology and tumorigenesis but how epithelial hormone receptor signaling and ECM are linked mechanistically is unclear. We identify the secreted protease Adamts18 as critical intermediary. Luminal estrogen and progesterone receptor signaling via upregulation of Wnt4 expression and ensuing canonical Wnt signaling activation in basal cells control Adamts18 expression there. The protease has an epithelial-intrinsic role in stem cell activation. We identify multiple binding partners in the interstitial ECM and BM and show that ADAMTS18 cleaves fibronectin in vitro. Its deletion results in increased fibronectin, collagen I and IV, and laminin deposition in pubertal glands. Adamts18 interacts genetically with Col18a1, which encodes a proteoglycan that is BM-specific, in stem cell regulation. Adamts18 inactivation impairs Hippo signaling and reduces Fgfr2 expression and signaling, which are vital for stem cell function. Our findings link epithelial hormone signaling to BM remodeling by Adamts18, and define the BM as an essential stem cell niche component.

2020-02-22 | GSE145717 | GEO

The secreted protease Adamts18 links mammary epithelial hormone action to extracellular matrix changes and stem cell niche function

2020-02-22 | GSE145680 | GEO

The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche.

Project description:Estrogens and progesterone control breast development and carcinogenesis via their cognate receptors expressed in a subset of luminal cells in the mammary epithelium. How they control the extracellular matrix, important to breast physiology and tumorigenesis, remains unclear. Here we report that both hormones induce the secreted protease Adamts18 in myoepithelial cells by controlling Wnt4 expression with consequent paracrine canonical Wnt signaling activation. Adamts18 is required for stem cell activation, has multiple binding partners in the basement membrane and interacts genetically with the basal membrane-specific proteoglycan, Col18a1, pointing to the basement membrane as part of the stem cell niche. In vitro, ADAMTS18 cleaves fibronectin; in vivo, Adamts18 deletion causes increased collagen deposition during puberty, which results in impaired Hippo signaling and reduced Fgfr2 expression both of which control stem cell function. Thus, Adamts18 links luminal hormone receptor signaling to basement membrane remodeling and stem cell activation.

| S-EPMC7099066 | biostudies-literature

The Lon protease links nucleotide metabolism with proteotoxic stress

Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived transcriptome profiling (RNA-seq) and transposon insertion mutagenesis (Tnseq) libraries of Lon deletions compared to wt Caulobacter crescentus. Methods: See Methods section of The Lon protease links nucleotide metabolism with proteotoxic stress for information regarding methods or contact lead correspondence. Briefly, Samples for RNAseq were extracted from wt and lon deletion strains grown to mid exponential phase. Methods: See Methods section of The Lon protease links nucleotide metabolism with proteotoxic stress for information regarding methods or contact lead correspondence. Briefly, Samples for Tnseq were generated by Eztn5 transposon mutagenesis. Conclusions: Our study represents the first detailed analysis of lon deletion comparison to wt caulobacter transcriptomes, with biologic replicates, generated by RNA-seq technology.

2020-06-14 | GSE152426 | GEO

The Lon protease links nucleotide metabolism with proteotoxic stress

Project description:The Lon protease links nucleotide metabolism with proteotoxic stress

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Protease-activated receptor 2 links protease activity with calcium waves during egg activation and blastomere cleavage

Project description:Protease-activated receptor 2 links protease activity with calcium waves during egg activation and blastomere cleavage

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Protease-activated receptor 2 links protease activity with calcium waves during egg activation and blastomere cleavage

Project description:Successful initiation of animal development requires activation of the egg immediately prior to fusion of gamete pronucleii. In all taxa, this is initiated by waves of calcium transients which transverse across the egg. Calcium waves also occur at cleavage furrows during later blastula cytokinesis. Calcium is released from the endoplasmic reticulum through activation of 1,4,5-trisphosphate (IP3) receptors. Only a subset of the mechanisms employed to generate IP3 during vertebrate egg activation are defined, with strong evidence that other critical mechanisms exist. Serine proteases have been long implicated in egg activation and fertilisation. Here we report that treatment of zebrafish eggs with serine protease inhibitors leads to defective calcium wave propagation and failed egg activation. We further show that mutation of zebrafish Protease-activated receptor 2a (Par2a) also results in severe disruption of egg activation, leading to failed chorion elevation and ooplasmic segregation. Milder par2a mutants progress further, but then show abnormal blastomere cleavage. We observed that par2a mutants show decreased amplitude and duration of calcium transients. Restoring Ca++ or direct injection of IP3 ligand rescues egg activation aborted by either serine protease inhibitor treatment or by mutation of Par2a. We thus show that serine protease activity is a critical regulator of IP3 and subsequent calcium wave amplification during zebrafish egg activation, and link this to intracellular calcium release via the protease receptor, Par2a. This constitutes a novel signalling pathway critical for successful fertilisation.

2025-03-29 | GSE289416 | GEO

Secreted phosphoprotein 1 expression in retinal mononuclear phagocytes links murine to human choroidal neovascularization

Project description:Secreted phosphoprotein 1 expression in retinal mononuclear phagocytes links murine to human choroidal neovascularization

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Protease Treatment

Project description:Determine if transcripts are released by protease treatment Keywords: Comparison of protease treatments

2005-12-01 | GSE3686 | GEO