Evidence map›Paper›PMID 37958795›Full record

ArticleInternational journal of molecular sciences2023

Nε-Carboxymethyl-Lysine Modification of Extracellular Matrix Proteins Augments Fibroblast Activation.

Harshavardhana H Ediga, Patrick Hester, Adithi Yepuri, Geereddy Bhanuprakash Reddy, Satish K Madala

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. High glucose enhances NScientific reports · 2026
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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 2 institutions in 2 countries.

Harshavardhana H EdigaDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267-0564, USA.ORCID 0000-0002-2809-5449
Patrick HesterDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267-0564, USA.
Adithi YepuriDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267-0564, USA.
Geereddy Bhanuprakash ReddyDepartment of Biochemistry, ICMR-National Institute of Nutrition, Hyderabad 500007, India.ORCID 0000-0003-4787-3944
Satish K MadalaDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267-0564, USA.ORCID 0000-0002-6042-5321
University of Cincinnati · USNational Institute of Nutrition · IN

Funding

WT1 REGULATION OF PULMONARY FIBROSISR01HL134801 · NHLBI · UNIVERSITY OF CINCINNATI · PI MADALA, SATISH K · 2017 to 2025
$3.9M
Sox9 Regulation of Fibroblast Activation and Pulmonary FibrosisR01HL157176 · NHLBI · UNIVERSITY OF CINCINNATI · PI MADALA, SATISH K · 2021 to 2025
$2.5M
NHLBI NIH HHS R01 HL134801NHLBI NIH HHS R01 HL157176
6 · The paper itself

Abstract

The extracellular matrix (ECM) is a dynamic complex protein network that provides structural integrity and plays an active role in shaping fibroblast behavior both in health and disease. Despite its essential functions, the impact of age-associated post-translational modifications on ECM-driven fibroblast activities such as proliferation, survival, fibroblast-to-myofibroblast transformation (FMT), and extracellular matrix production remains largely unknown. Nε-carboxymethyl-lysine (CML) is one of the well-characterized advanced glycation end-products (AGEs) that can occur on lysine residues within ECM proteins through non-enzymatic glycation. In this study, we determined the accumulation and the effects of the CML-modified ECM (CML-ECM) on fibroblast activation. Immunostainings and immunoblot analysis demonstrated significant increases in CML-AGE content in idiopathic pulmonary fibrosis (IPF) compared to age-matched healthy lungs. Gene expression analysis and fibroblast activation assays collectively implicate the ECM as a negative regulator of fibroblast activation. Notably, the CML modification of the ECM resulted in a significant decrease in its anti-fibrotic effects including proliferation, FMT, apoptosis, and ECM production. Together, the results of this study revealed an unexplored pathological role played by the CML-ECM on fibroblast activation, which has wide implications in IPF and other fibrotic diseases.

Indexed as

Extracellular Matrix ProteinsIdiopathic Pulmonary FibrosisExtracellular MatrixFibroblastsFibrosisGlycation End Products, AdvancedHumansLysineExtracellular Matrix ProteinsGlycation End Products, AdvancedLysineN(6)-carboxymethyllysineadvanced glycation end productsextracellular matrixidiopathic pulmonary fibrosismyofibroblast transformationNε-carboxymethyl-lysine

Identifiers

PMID37958795
PMCPMC10650592
OpenAlexW4388088682

What Socratic 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 Socratic graph.