Evidence map›Paper›PMID 33288795›Full record

ArticleScientific reports2020

Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton.

Sade W Clayton, Ga I Ban, Cunren Liu, Rosa Serra

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

35 citing papers in PubMed, 66 citations in OpenAlex.

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  20. Proactive and reactive roles of TGF-β in cancer.Seminars in cancer biology · 2023
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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

4 authors at 2 institutions in 1 country.

Sade W ClaytonDepartment of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, 660 MCLM, 1918 University Blvd., Birmingham, Al, 35294-0005, USA.
Ga I BanDepartment of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, 660 MCLM, 1918 University Blvd., Birmingham, Al, 35294-0005, USA.
Cunren LiuDepartment of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, 660 MCLM, 1918 University Blvd., Birmingham, Al, 35294-0005, USA.
Rosa SerraDepartment of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, 660 MCLM, 1918 University Blvd., Birmingham, Al, 35294-0005, USA. rserra@uab.edu.
University of Alabama at Birmingham · USDuke University Hospital · US

Funding

TGF-Beta in the Pathology and Development of the SpineR01AR053860 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SERRA, ROSA A. · 2007 to 2017
$3.2M
Training Program in Rheumatic and Musculoskeletal Diseases ResearchT32AR069516 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI John D Mountz · 2016 to 2026
$2.6M
TGF-beta in the Pathology and Development of the SpineR56AR053860 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SERRA, ROSA A. · 2020 to 2020
$426k
NIAMS NIH HHS R01 AR053860NIAMS NIH HHS R56 AR053860NIAMS NIH HHS T32 AR069516NIH HHS R01 AR053860
6 · The paper itself

Abstract

Previously, we showed that embryonic deletion of TGF-β type 2 receptor in mouse sclerotome resulted in defects in fibrous connective tissues in the spine. Here we investigated how TGF-β regulates expression of fibrous markers: Scleraxis, Fibromodulin and Adamtsl2. We showed that TGF-β stimulated expression of Scleraxis mRNA by 2 h and Fibromodulin and Adamtsl2 mRNAs by 8 h of treatment. Regulation of Scleraxis by TGF-β did not require new protein synthesis; however, protein synthesis was required for expression of Fibromodulin and Adamtsl2 indicating the necessity of an intermediate. We subsequently showed Scleraxis was a potential intermediate for TGF-β-regulated expression of Fibromodulin and Adamtsl2. The canonical effector Smad3 was not necessary for TGF-β-mediated regulation of Scleraxis. Smad3 was necessary for regulation of Fibromodulin and Adamtsl2, but not sufficient to super-induce expression with TGF-β treatment. Next, the role of several noncanonical TGF-β pathways were tested. We found that ERK1/2 was activated by TGF-β and required to regulate expression of Scleraxis, Fibromodulin, and Adamtsl2. Based on these results, we propose a model in which TGF-β regulates Scleraxis via ERK1/2 and then Scleraxis and Smad3 cooperate to regulate Fibromodulin and Adamtsl2. These results define a novel signaling mechanism for TGFβ-mediated fibrous differentiation in sclerotome.

Indexed as

ADAMTS ProteinsAnimalsBasic Helix-Loop-Helix ProteinsBlotting, WesternBone DevelopmentCell DifferentiationExtracellular Matrix ProteinsFemaleFibromodulinMaleMiceMice, Inbred C57BLPregnancyReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingAdamtsl2 protein, mouseADAMTS ProteinsBasic Helix-Loop-Helix ProteinsExtracellular Matrix ProteinsFibromodulinFmod protein, mouseRNA, MessengerRNA, Small InterferingScx protein, mouseTransforming Growth Factor beta

Identifiers

PMID33288795
PMCPMC7721728
OpenAlexW3112412250

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.