PuSH - Publication Server of Helmholtz Zentrum München: TRPM7 restrains plasmin activity and promotes transforming growth factor-β1 signaling in primary human lung fibroblasts.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Zeitlmayr, S.* ; Zierler, S.* ; Staab-Weijnitz, C.A. ; Dietrich, A.* ; Geiger, F.* ; Horgen, F.D.* ; Gudermann, T.* ; Breit, A.*

TRPM7 restrains plasmin activity and promotes transforming growth factor-β1 signaling in primary human lung fibroblasts.

Arch. Toxicol. 96, 2767-2783 (2022)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Hybrid

Abstract
Metrics
Extra information

Sustained exposure of the lung to various environmental or occupational toxins may eventually lead to pulmonary fibrosis, a devastating disease with no cure. Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix (ECM) proteins such as fibronectin and collagens. The peptidase plasmin degrades the ECM, but protein levels of the plasmin activator inhibitor-1 (PAI-1) are increased in fibrotic lung tissue, thereby dampening plasmin activity. Transforming growth factor-β1 (TGF-β1)-induced activation of SMAD transcription factors promotes ECM deposition by enhancing collagen, fibronectin and PAI-1 levels in pulmonary fibroblasts. Hence, counteracting TGF-β1-induced signaling is a promising approach for the therapy of pulmonary fibrosis. Transient receptor potential cation channel subfamily M Member 7 (TRPM7) supports TGF-β1-promoted SMAD signaling in T-lymphocytes and the progression of fibrosis in kidney and heart. Thus, we investigated possible effects of TRPM7 on plasmin activity, ECM levels and TGF-β1 signaling in primary human pulmonary fibroblasts (pHPF). We found that two structurally unrelated TRPM7 blockers enhanced plasmin activity and reduced fibronectin or PAI-1 protein levels in pHPF under basal conditions. Further, TRPM7 blockade strongly inhibited fibronectin and collagen deposition induced by sustained TGF-β1 stimulation. In line with these data, inhibition of TRPM7 activity diminished TGF-β1-triggered phosphorylation of SMAD-2, SMAD-3/4-dependent reporter activation and PAI-1 mRNA levels. Overall, we uncover TRPM7 as a novel supporter of TGF-β1 signaling in pHPF and propose TRPM7 blockers as new candidates to control excessive ECM levels under pathophysiological conditions conducive to pulmonary fibrosis.

Impact Factor

Scopus SNIP

Altmetric

6.168

0.000