AI Article Synopsis

  • CCN2/CTGF is a protein that is linked to kidney fibrosis and is produced in excess in progressive renal diseases.
  • Research shows that blocking CCN2 can reduce kidney damage and ECM buildup by affecting the EGFR pathway, which is crucial in inflammation and fibrosis.
  • Studies on mice indicate that inhibiting the EGFR can lessen fibrotic responses caused by CCN2, suggesting that targeting this pathway might be a promising treatment for renal diseases associated with fibrosis.

Article Abstract

Connective tissue growth factor (CCN2/CTGF) is a matricellular protein that is overexpressed in progressive human renal diseases, mainly in fibrotic areas. In vitro studies have demonstrated that CCN2 regulates the production of extracellular matrix (ECM) proteins and epithelial-mesenchymal transition (EMT), and could therefore contribute to renal fibrosis. CCN2 blockade ameliorates experimental renal damage, including diminution of ECM accumulation. We have reported that CCN2 and its C-terminal degradation product CCN2(IV) bind to epidermal growth factor receptor (EGFR) to modulate renal inflammation. However, the receptor involved in CCN2 profibrotic actions has not been described so far. Using a murine model of systemic administration of CCN2(IV), we have unveiled a fibrotic response in the kidney that was diminished by EGFR blockade. Additionally, in conditional CCN2 knockout mice, renal fibrosis elicited by folic acid-induced renal damage was prevented, and this was linked to inhibition of EGFR pathway activation. Our in vitro studies demonstrated a direct effect of CCN2 via the EGFR pathway on ECM production by fibroblasts and the induction of EMT in tubular epithelial cells. Our studies clearly show that the EGFR regulates CCN2 fibrotic signalling in the kidney, and suggest that EGFR pathway blockade could be a potential therapeutic option to block CCN2-mediated profibrotic effects in renal diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Download full-text PDF

Source
http://dx.doi.org/10.1002/path.5007DOI Listing

Publication Analysis

Top Keywords

growth factor
16
renal fibrosis
12
egfr pathway
12
connective tissue
8
tissue growth
8
renal
8
epidermal growth
8
factor receptor
8
renal diseases
8
vitro studies
8

Similar Publications

Background: The Yunnan-Guizhou Plateau's high-altitude setting is characterized by intense solar ultraviolet radiation, a significant environmental stressor that frequently leads to skin barrier damage. This damage presents clinically as erythema, itching, and desquamation, underscoring the need for effective reparative interventions.

Aims: The objective of this study was to assess the therapeutic efficacy of a novel treatment protocol that integrates non-crosslinked hyaluronic acid (HA) injection with microneedle application of human epidermal growth factor (hEGF) for the restoration of skin barrier function in regions of high altitude.

View Article and Find Full Text PDF

Background: Longitudinal studies of family carers of people with intellectual disabilities during the COVID-19 pandemic have been very rare. This study investigated trajectories of family-carer wellbeing and the impact of the caring role on carers' health over four time points measured during the COVID-19 pandemic and after all public health restrictions had been lifted (between December 2020 and late 2022) across the United Kingdom.

Methods: Family carers of adults with intellectual disabilities participated through a co-designed, online survey at four time points across the pandemic (2020-2022).

View Article and Find Full Text PDF

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the TUNEL assay data shown in Fig. 4B were strikingly similar to data appearing in different form in another article written by different authors at different research institutes that had already been submitted for publication to the journal (which has subsequently been retracted). Owing to the fact that these contentious data had already apparently been submitted for publication prior to the receipt of this paper to , the Editor has decided that this paper should be retracted from the Journal.

View Article and Find Full Text PDF

Osteoarthritis (OA) is a common joint disorder involving the cartilage and other joint tissues. Quercetin (QCT) serves a protective role in the development of OA. However, to the best of our knowledge, the regulatory mechanisms of QCT in the progression of OA have not yet been fully elucidated.

View Article and Find Full Text PDF

New phthalazine-derived inhibitors for VEGFR-2 were synthesized for anticancer evaluations. Also, docking studies were performed to explore the suggested binding orientations of the novel derivatives inside the binding site of VEGFR-2. The achieved biological data were extremely interrelated to that of docking study.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: