Evidence map›Paper›PMID 33648801›Full record

ArticleJournal of dermatological science2021

Age-related elevation of HGF is driven by the reduction of fibroblast size in a YAP/TAZ/CCN2 axis-dependent manner.

Yaping Xiang, Zhaoping Qin, Yan Yang, Gary J Fisher, Taihao Quan

Open access · greenAbstract read
In one paragraph

Article in Journal of dermatological science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Yaping XiangDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Zhaoping QinDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Yan YangDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Gary J FisherDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Taihao QuanDepartment of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: thquan@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Control of aging and age-related diseases by extracellular matrix microenvironmentR01AG054835 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FISHER, GARY J, QUAN, TAIHAO · 2017 to 2021
$1.7M
Role of dermal extracellular matrix microenvironment in skin agingR01AG051849 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FISHER, GARY J, QUAN, TAIHAO · 2016 to 2020
$1.6M
NIA NIH HHS R01 AG051849NIA NIH HHS R01 AG054835
6 · The paper itself

Abstract

backgroundAged human skin is primarily attributable to the loss of collagen. Hepatocyte growth factor (HGF) acts as an anti-fibrotic factor by suppression of collagen production. In aged human skin, HGF is elevated in dermal fibroblasts and thus contributes to dermal aging (thin dermis) by suppression of collagen production.

objectiveWe aimed to investigate the underlying mechanisms of age-related elevation of HGF expression.

methodsCollagen fibrils in the aged skin dermis are fragmented and disorganized, which impairs collagen-fibroblast interaction, resulting in reduced fibroblast spreading and size. To explore the connection between reduced dermal fibroblast size and age-related elevation of HGF expression, we manipulate dermal fibroblast size, and cell-size dependent regulation of HGF was investigated by laser capture microdissection, immunostaining, capillary electrophoresis immunoassay, and quantitative RT-PCR.

resultsWe found that reduced fibroblast size is responsible for age-related elevation of HGF expression. Further investigation indicated that cell size-dependent upregulation of HGF expression was mediated by impeded YAP/TAZ nuclear translocation and their target gene, CCN2. Conversely, restoration of dermal fibroblast size rapidly reversed cell-size-dependent upregulation of HGF in a YAP/TAZ-dependent manner. Finally, we confirmed that elevated HGF expression is accompanied by the reduced expression of YAP/TAZ and CCN2 in the aged human skin in vivo.

conclusionAge-related elevation of HGF is driven by the reduction of fibroblast size in a YAP/TAZ/CCN2 axis-dependent manner. These data reveal a novel mechanism by which reduction of fibroblast size upregulates HGF expression, which in turn contributes to loss of collagen, a prominent feature of aged human skin.

Indexed as

Adaptor Proteins, Signal TransducingAdultAged, 80 and overBiopsyCells, CulturedCell SizeCollagenConnective Tissue Growth FactorFibroblastsGene Expression RegulationHepatocyte Growth FactorHumansIntracellular Signaling Peptides and ProteinsPrimary Cell CultureSignal TransductionSkinAdaptor Proteins, Signal TransducingCCN2 protein, humanCollagenConnective Tissue Growth FactorHepatocyte Growth FactorHGF protein, humanIntracellular Signaling Peptides and ProteinsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsWWTR1 protein, humanYAP1 protein, humanYAP-Signaling ProteinsCCN2Cell sizeDermal agingHGFYAP/TAZ

Identifiers

PMID33648801
PMCPMC8131214
OpenAlexW3129384848

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.