Dipeptidyl peptidase-4-mediated fibronectin processing evokes a pro-fibrotic extracellular matrix
Abstract: Fibronectin serves as a platform to guide and facilitate deposition of collagen and fibrillin microfibrils. During development of fibrotic diseases, altered fibronectin deposition in the extracellular matrix (ECM) is generally an early event. After this, dysregulated organization of fibrillins and fibrillar collagens occurs. Because fibronectin is an essential orchestrator of healthy ECM, perturbation of its ECM-organizational capacity may be involved in development of fibrosis. To investigate this, we employed recessive dystrophic epidermolysis bullosa as a disease model with progressive, severe dermal fibrosis. Fibroblasts from donors with recessive dystrophic epidermolysis bullosa in 2-dimensional and 3-dimensional cultures displayed dysregulated fibronectin deposition. Our analyses revealed that increase of profibrotic dipeptidyl peptidase-4–positive fibroblasts coincides with altered fibronectin deposition. Dipeptidyl peptidase-4 inhibitors normalized deposition of fibronectin and subsequently of fibrillin microfibrils and collagen I. Intriguingly, proteomics and inhibitor and mutagenesis studies disclosed that dipeptidyl peptidase-4 modulates ECM deposition through the proteolysis of the fibronectin N-terminus. Our study provides mechanistic insights into the observed profibrotic activities of dipeptidyl peptidase-4 and extends the understanding of fibronectin-guided ECM assembly in health and disease
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Notes
-
The journal of investigative dermatology. - 144, 11 (2024) , 2477-2487.e13, ISSN: 0022-202X
- Event
-
Veröffentlichung
- (where)
-
Freiburg
- (who)
-
Universität
- (when)
-
2024
- Creator
-
Zeyer, Karina
Bornert, Olivier
Nelea, Valentin
Bao, Xinyi
Leytens, Alexandre
Sharoyan, Svetlana
Sengle, Gerhard
Antonyan, Alvard
Bruckner-Tuderman, Leena
Dengjel, Jörn
Reinhardt, Dieter P.
Nyström, Alexander
- DOI
-
10.1016/j.jid.2024.03.020
- URN
-
urn:nbn:de:bsz:25-freidok-2463346
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
17.04.2025, 3:17 PM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Zeyer, Karina
- Bornert, Olivier
- Nelea, Valentin
- Bao, Xinyi
- Leytens, Alexandre
- Sharoyan, Svetlana
- Sengle, Gerhard
- Antonyan, Alvard
- Bruckner-Tuderman, Leena
- Dengjel, Jörn
- Reinhardt, Dieter P.
- Nyström, Alexander
- Universität
Time of origin
- 2024
Other Objects (12)
The MHC II ligandome : mass spectrometric applications in immunology = Das MHC-II-Ligandom
Autophagosomal protein dynamics and influenza virus infection
Analyses of fibroblasts associated with chronic wounds suggest a major role in chronic wound pathophysiology
Dietary spermidine for lowering high blood pressure
The mTOR pathway controls phosphorylation of BRAF at T401
The mTOR pathway controls phosphorylation of BRAF at T401
O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts
Dipeptidylpeptidase-4-mediated fibronectin interaction promotes deposition of a profibrotic extracellular matrix
Regulation of fibroblast Fas expression by soluble and mechanical pro-fibrotic stimuli
Early activation of pro-fibrotic WNT5A in sepsis-induced acute lung injury
Increased abundance of Cbl E3 ligases alters PDGFR signaling in recessive dystrophic epidermolysis bullosa
Control of RAB 7 activity and localization through the retromer‐TBC1D5 complex enables RAB 7‐dependent mitophagy
The MHC II ligandome : mass spectrometric applications in immunology = Das MHC-II-Ligandom
Autophagosomal protein dynamics and influenza virus infection
Analyses of fibroblasts associated with chronic wounds suggest a major role in chronic wound pathophysiology
Dietary spermidine for lowering high blood pressure
The mTOR pathway controls phosphorylation of BRAF at T401
The mTOR pathway controls phosphorylation of BRAF at T401
O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts
Dipeptidylpeptidase-4-mediated fibronectin interaction promotes deposition of a profibrotic extracellular matrix
Regulation of fibroblast Fas expression by soluble and mechanical pro-fibrotic stimuli
Early activation of pro-fibrotic WNT5A in sepsis-induced acute lung injury
Increased abundance of Cbl E3 ligases alters PDGFR signaling in recessive dystrophic epidermolysis bullosa
Control of RAB 7 activity and localization through the retromer‐TBC1D5 complex enables RAB 7‐dependent mitophagy
The MHC II ligandome : mass spectrometric applications in immunology = Das MHC-II-Ligandom
Autophagosomal protein dynamics and influenza virus infection
Analyses of fibroblasts associated with chronic wounds suggest a major role in chronic wound pathophysiology
Dietary spermidine for lowering high blood pressure
The mTOR pathway controls phosphorylation of BRAF at T401
The mTOR pathway controls phosphorylation of BRAF at T401
O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts
Dipeptidylpeptidase-4-mediated fibronectin interaction promotes deposition of a profibrotic extracellular matrix
Regulation of fibroblast Fas expression by soluble and mechanical pro-fibrotic stimuli
Early activation of pro-fibrotic WNT5A in sepsis-induced acute lung injury
Increased abundance of Cbl E3 ligases alters PDGFR signaling in recessive dystrophic epidermolysis bullosa