The Crosstalk between N-Formyl Peptide Receptors and uPAR in Systemic Sclerosis : Molecular Mechanisms, Pathogenetic Role and Therapeutic Opportunities
Systemic Sclerosis (SSc) is a heterogeneous autoimmune disease characterized by widespread vasculopathy, the presence of autoantibodies and the progressive fibrosis of skin and visceral organs. There are still many questions about its pathogenesis, particularly related to the complex regulation of the fibrotic process, and to the factors that trigger its onset. Our recent studies supported a key role of N-formyl peptide receptors (FPRs) and their crosstalk with uPAR in the fibrotic phase of the disease. Here, we found that dermal fibroblasts acquire a proliferative phenotype after the activation of FPRs and their interaction with uPAR, leading to both Rac1 and ERK activation, c-Myc phosphorylation and Cyclin D1 upregulation which drive cell cycle progression. The comparison between normal and SSc fibroblasts reveals that SSc fibroblasts exhibit a higher proliferative rate than healthy control, suggesting that an altered fibroblast proliferation could contribute to the initiation and progression of the fibrotic process. Finally, a synthetic compound targeting the FPRs/uPAR interaction significantly inhibits SSc fibroblast proliferation, paving the way for the development of new targeted therapies in fibrotic diseases.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 25(2024), 6 vom: 09. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Napolitano, Filomena [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Autoantibodies |
|---|
| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 30.03.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms25063156 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370316797 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370316797 | ||
| 003 | DE-627 | ||
| 005 | 20240331001818.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240329s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms25063156 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1357.xml |
| 035 | |a (DE-627)NLM370316797 | ||
| 035 | |a (NLM)38542130 | ||
| 035 | |a (PII)3156 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Napolitano, Filomena |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Crosstalk between N-Formyl Peptide Receptors and uPAR in Systemic Sclerosis |b Molecular Mechanisms, Pathogenetic Role and Therapeutic Opportunities |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 29.03.2024 | ||
| 500 | |a Date Revised 30.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Systemic Sclerosis (SSc) is a heterogeneous autoimmune disease characterized by widespread vasculopathy, the presence of autoantibodies and the progressive fibrosis of skin and visceral organs. There are still many questions about its pathogenesis, particularly related to the complex regulation of the fibrotic process, and to the factors that trigger its onset. Our recent studies supported a key role of N-formyl peptide receptors (FPRs) and their crosstalk with uPAR in the fibrotic phase of the disease. Here, we found that dermal fibroblasts acquire a proliferative phenotype after the activation of FPRs and their interaction with uPAR, leading to both Rac1 and ERK activation, c-Myc phosphorylation and Cyclin D1 upregulation which drive cell cycle progression. The comparison between normal and SSc fibroblasts reveals that SSc fibroblasts exhibit a higher proliferative rate than healthy control, suggesting that an altered fibroblast proliferation could contribute to the initiation and progression of the fibrotic process. Finally, a synthetic compound targeting the FPRs/uPAR interaction significantly inhibits SSc fibroblast proliferation, paving the way for the development of new targeted therapies in fibrotic diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a N-formyl peptide receptors | |
| 650 | 4 | |a fibroblast proliferation | |
| 650 | 4 | |a small molecules | |
| 650 | 4 | |a systemic sclerosis | |
| 650 | 4 | |a urokinase receptor | |
| 650 | 7 | |a Receptors, Formyl Peptide |2 NLM | |
| 650 | 7 | |a Autoantibodies |2 NLM | |
| 700 | 1 | |a Rossi, Francesca Wanda |e verfasserin |4 aut | |
| 700 | 1 | |a de Paulis, Amato |e verfasserin |4 aut | |
| 700 | 1 | |a Lavecchia, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Montuori, Nunzia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 25(2024), 6 vom: 09. März |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:25 |g year:2024 |g number:6 |g day:09 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms25063156 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 25 |j 2024 |e 6 |b 09 |c 03 | ||