Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ANKRD1 promotes cell migration by suppressing ELN production during early senescence

ABSTRACT: Cellular senescence is a complex biological process that contributes to wound healing, carcinogenesis, and age-related disease. Although the molecular mechanisms whereby senescence promotes wound repair are not well understood, the protein ANKRD1, which promoted wound healing in mice, was found to increase in senescent cells. We hypothesized that ANKRD1 may play a role in senescence-mediated wound healing. Conditioned medium (CM) from senescent WI-38 human diploid fibroblasts hastened cell migration of human HaCaT keratinocytes. Interestingly, silencing ANKRD1 in WI-38 cells reduced the effect of CM on cell migration, while overexpressing ANKRD1 accelerated it. Further proteomic analysis revealed that ANKRD1 associates with YBOX1, a multifunctional protein that modulates transcription of the ELN gene and reduces ELN mRNA production. The product of the ELN gene, the protein ELN or tropoelastin (a subunit of elastin), is a secreted factor that reduces motility. Thus, we propose that a rise in ANKRD1 during early senescence transiently limits the YBOX1-dependent transcriptional increase in ELN production, and thereby enables cell motility in early phases of senescence.

INSTRUMENT(S): NA

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Myriam Gorospe

PROVIDER: MSV000092079 | MassIVE | Thu Jun 01 09:27:00 BST 2023

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptomic datat of senescence WI-38 cell

Project description:Senescence in WI-38 cell context was induce by RASv12 over expression Cellular senescence is a permanent cell cycle arrest that is triggered by cancer- initiating or promoting events in mammalian cells and is now considered a major tumour suppressor mechanism. Here, we did a transcriptomic analysis and compared WI-38 contol wich is a human fibroblaste cell line and WI-38 that overexpressed RASv12 a G protein that induce senescence. The goal of our project is to compare transciptomic profile of human growing fibroblast (WI-38 control) and senescent human fibroblast (WI-38 OERAS)

2011-11-16 | GSE33710 | GEO

Transcriptomic datat of senescence WI-38 cell

2011-11-16 | E-GEOD-33710 | biostudies-arrayexpress

Senescence-associated lncRNAs: senescence-associated long noncoding RNAs.

Project description:Noncoding RNAs include small transcripts, such as microRNAs and piwi-interacting RNAs, and a wide range of long noncoding RNAs (lncRNAs). Although many lncRNAs have been identified, only a small number of lncRNAs have been characterized functionally. Here, we sought to identify lncRNAs differentially expressed during replicative senescence. We compared lncRNAs expressed in proliferating, early-passage, 'young' human diploid WI-38 fibroblasts [population doubling (PDL) 20] with those expressed in senescent, late-passage, 'old' fibroblasts (PDL 52) by RNA sequencing (RNA-Seq). Numerous transcripts in all lncRNA groups (antisense lncRNAs, pseudogene-encoded lncRNAs, previously described lncRNAs and novel lncRNAs) were validated using reverse transcription (RT) and real-time, quantitative (q)PCR. Among the novel senescence-associated lncRNAs (SAL-RNAs) showing lower abundance in senescent cells, SAL-RNA1 (XLOC_023166) was found to delay senescence, because reducing SAL-RNA1 levels enhanced the appearance of phenotypic traits of senescence, including an enlarged morphology, positive Î²-galactosidase activity, and heightened p53 levels. Our results reveal that the expression of known and novel lncRNAs changes with senescence and suggests that SAL-RNAs play direct regulatory roles in this important cellular process. RNA was extracted from both young and senescent WI-38 cells and used for total RNA-Seq.

2016-02-08 | E-GEOD-77675 | biostudies-arrayexpress

Global microarray analysis of changes of gene expression in the epidermis of K14-caSmad1 mice

Project description:Bone morphogenetic protein (BMP) signalling plays a key role in the control of skin development and postnatal remodelling by regulating keratinocyte proliferation, differentiation and apoptosis. To study the role of BMPs in wound-induced epidermal repair, we used transgenic mice overexpressing the BMP downstream component Smad1 under the control of a K14 promoter as an in vivo model, as well as ex vivo and in vitro assays. K14-caSmad1 mice exhibited retarded wound healing associated with significant inhibition of proliferation and increased apoptosis in healing wound epithelium. Furthermore, microarray and qRT-PCR analyses revealed decreased expression of a number of cytoskeletal/cell motility-associated genes including wound-associated keratins (Krt16, Krt17) and Myo5a, in the epidermis of K14- caSmad1 mice versus wild-type controls during wound healing. BMP treatment significantly inhibited keratinocyte migration ex vivo, and primary keratinocytes of K14-caSmad1 mice showed retarded migration compared to wild-type controls. Finally, siRNA-mediated silencing of Bmpr-1B in primary mouse keratinocytes accelerated cell migration and was associated with increased expression of Krt16, Krt17 and Myo5a compared to controls. Thus, this study demonstrates that BMPs inhibit keratinocyte proliferation, cytoskeletal organization and migration in regenerating skin epithelium during wound healing, and raises a possibility for using BMP antagonists for the management of chronic wounds. Two-condition experiment, Wild type vs. Smad1 overexpressing mice. Biological replicates: 2 replicates.

2013-11-01 | E-GEOD-50578 | biostudies-arrayexpress

ANT2 accelerates cutaneous wound healing in aged skin by reverse senescence

Project description:An effective healing response is critical to healthy aging. Thus, the connection of regeneration and aging is needed to understand the complicated age-related healing process. Energy metabolism has been a common hallmark of both studies. In recent years, it become an emerging factor of skin homeostasis. Adenine nucleotide translocase-2 (ANT2) is a known cell proliferation marker and mediator of ATP import into mitochondria for energy homeostasis. Although energy homeostasis and the maintenance of mitochondrial function are critical for wound healing, the role of ANT2 in wound healing has not been elucidated. We found that ANT2 expression decreased during aging in mouse skin as well as during cellular senescence. Interestingly, overexpression of ANT2 in aged mouse skin promoted the healing of full-thickness cutaneous wounds. In addition, upregulation of ANT2 in replicative senescent human diploid dermal fibroblasts (HDFs) induced cell proliferation and migration, which are critical for the wound healing process. Furthermore, overexpression of ANT2 increased ATP production rate by activating the glycolysis pathway and also increased mitophagy, both of which are involved in energy homeostasis. Notably, ANT2-mediated upregulation of HSPA6 in aged HDFs inhibited the expression of pro-inflammatory genes that mediate cellular senescence and mitochondrial damage. This study demonstrates a new physiological role of ANT2 in skin wound healing via regulation of cell proliferation, energy homeostasis, and inflammation. Thus, our study links energy metabolism to skin homeostasis and identifies a genetic factor for improving wound healing with aging model.

2022-11-21 | GSE206141 | GEO

The whole transcriptome analysis in a replicative senescence model.

Project description:RNA-Seq was performed to screen transcripts in whole lyastes or mitoplast fraction prepared from young and senescent WI-38 human fibroblast

2016-09-12 | GSE73458 | GEO

p53- repressed miRNAs are involved with E2F in a feed forward loop promoting proliferation

Project description:There is a distinctive miRNA expression profile between early (young) and replicative senescence (old). We observed a cluster of miRNAs that were repressed upon senescence in both MRC-5 and WI-38 fibroblast cells. miRNAs profiling in young and senescence human emryonic fibroblasts (MRC-5 and WI-38)

2010-05-19 | E-GEOD-12821 | biostudies-arrayexpress

Oxylipin biosynthesis reinforces cellular senescence through a RAS/p53 feedback loop and allows detection of senolysis

Project description:Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation and many age-related pathologies. By contrast, lipid components of the SASP are understudied. We show that senescent cells activate the biosynthesis of several oxylipins that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize and accumulate an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2. Released 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in vivo. This and other prostaglandin D2-related lipids promote the senescence arrest and SASP by activating RAS signaling. These data identify an important aspect of cellular senescence and a method to detect senolysis

2021-02-20 | ST001708 | MetabolomicsWorkbench

Transcriptome Signature of Cellular Senescence

Project description:Abstract: Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage, and signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damage, and β-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells. To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across 8 diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRASG12V. The intersection of the altered transcriptomes revealed 47 RNAs consistently elevated and 26 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some long noncoding RNAs. We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancy, and the development of strategies to target senescent cells therapeutically.

2019-06-12 | GSE130727 | GEO