دورية أكاديمية
أعرض في EDS

The Crosstalk between N-Formyl Peptide Receptors and uPAR in Systemic Sclerosis: Molecular Mechanisms, Pathogenetic Role and Therapeutic Opportunities.

التفاصيل البيبلوغرافية
العنوان: The Crosstalk between N-Formyl Peptide Receptors and uPAR in Systemic Sclerosis: Molecular Mechanisms, Pathogenetic Role and Therapeutic Opportunities.
المؤلفون: Napolitano F; Department of Translational Medical Sciences, University of Naples Federico II, 80138 Naples, Italy., Rossi FW; Department of Translational Medical Sciences, University of Naples Federico II, 80138 Naples, Italy.; Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, 80131 Naples, Italy., de Paulis A; Department of Translational Medical Sciences, University of Naples Federico II, 80138 Naples, Italy.; Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, 80131 Naples, Italy., Lavecchia A; 'Drug Discovery' Laboratory, Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy., Montuori N; Department of Translational Medical Sciences, University of Naples Federico II, 80138 Naples, Italy.; Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, 80131 Naples, Italy.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Mar 09; Vol. 25 (6). Date of Electronic Publication: 2024 Mar 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Receptors, Formyl Peptide*/metabolism , Scleroderma, Systemic*/pathology, Humans ; Fibrosis ; Fibroblasts/metabolism ; Autoantibodies/metabolism ; Skin/metabolism ; Cells, Cultured
مستخلص: 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.
References: Front Cell Dev Biol. 2022 Apr 08;10:818616. (PMID: 35493073)
J Pers Med. 2020 Nov 16;10(4):. (PMID: 33207563)
Int J Mol Sci. 2023 Jan 16;24(2):. (PMID: 36675310)
Transl Res. 2019 Jul;209:77-89. (PMID: 30876809)
Cells. 2020 Dec 09;9(12):. (PMID: 33317149)
Front Immunol. 2018 Nov 13;9:2452. (PMID: 30483246)
J Exp Med. 1972 Jun 1;135(6):1351-62. (PMID: 4260235)
J Immunol. 2007 Dec 15;179(12):8112-21. (PMID: 18056353)
Clin Cancer Res. 2012 Oct 15;18(20):5546-53. (PMID: 23071356)
Blood. 2003 Sep 15;102(6):1966-77. (PMID: 12791666)
Immunopharmacol Immunotoxicol. 2006;28(1):103-27. (PMID: 16684671)
Sci Rep. 2017 Aug 24;7(1):9388. (PMID: 28839232)
Arthritis Res Ther. 2013;15(3):215. (PMID: 23796020)
Drug Discov Today. 2021 Apr;26(4):1076-1085. (PMID: 33486111)
Am J Pathol. 2007 Dec;171(6):1789-99. (PMID: 18055544)
Autoimmun Rev. 2019 Nov;18(11):102396. (PMID: 31520794)
Int J Mol Sci. 2022 May 28;23(11):. (PMID: 35682744)
Nat Rev Mol Cell Biol. 2010 Jan;11(1):23-36. (PMID: 20027185)
Ann Rheum Dis. 2014 Sep;73(9):1700-9. (PMID: 23852693)
Lancet. 2017 Oct 7;390(10103):1685-1699. (PMID: 28413064)
J Exp Clin Cancer Res. 2017 Dec 08;36(1):180. (PMID: 29216889)
Molecules. 2017 Mar 13;22(3):. (PMID: 28335409)
BMC Cell Biol. 2004 Dec 29;5(1):50. (PMID: 15625007)
Am J Pathol. 1990 Sep;137(3):585-91. (PMID: 1698026)
Sci Rep. 2019 May 2;9(1):6815. (PMID: 31048743)
Trends Immunol. 2018 Oct;39(10):815-829. (PMID: 30195466)
J Scleroderma Relat Disord. 2017 May-Aug;2(2):69-134. (PMID: 29270465)
Exp Eye Res. 2016 Jan;142:56-70. (PMID: 26192991)
Sci Rep. 2016 Aug 24;6:32231. (PMID: 27554193)
Nat Rev Rheumatol. 2020 Jan;16(1):11-31. (PMID: 31792399)
J Clin Med. 2022 Apr 20;11(9):. (PMID: 35566425)
Proc Natl Acad Sci U S A. 2020 Jun 16;117(24):13457-13467. (PMID: 32482868)
Transl Med UniSa. 2016 Nov 01;15:34-41. (PMID: 27896225)
J Immunol. 2015 Jun 1;194(11):5161-73. (PMID: 25917089)
Invest Ophthalmol Vis Sci. 2011 May 16;52(6):3160-5. (PMID: 21228377)
Pharmacol Rev. 2009 Jun;61(2):119-61. (PMID: 19498085)
J Cell Biochem. 2017 Jun;118(6):1300-1307. (PMID: 28075050)
Cancers (Basel). 2022 Jan 19;14(3):. (PMID: 35158766)
Front Immunol. 2018 Apr 04;9:574. (PMID: 29670612)
J Cell Sci. 2020 Jul 10;133(13):. (PMID: 32651236)
Front Pharmacol. 2014 Jan 21;4:174. (PMID: 24478701)
Arthritis Rheum. 2001 Jul;44(7):1667-76. (PMID: 11465719)
Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G723-8. (PMID: 21292997)
J Dermatol. 2024 Feb 6;:. (PMID: 38321641)
Arthritis Rheum. 2000 Oct;43(10):2230-9. (PMID: 11037882)
J Clin Med. 2021 Feb 01;10(3):. (PMID: 33535668)
Cancers (Basel). 2021 Apr 12;13(8):. (PMID: 33921488)
Front Immunol. 2021 Dec 02;12:780641. (PMID: 34925360)
معلومات مُعتمدة: MUR: P2022HB33K PRIN 2022 PNRR, Settore ERC: LS4
فهرسة مساهمة: Keywords: N-formyl peptide receptors; fibroblast proliferation; small molecules; systemic sclerosis; urokinase receptor
المشرفين على المادة: 0 (Receptors, Formyl Peptide)
0 (Autoantibodies)
تواريخ الأحداث: Date Created: 20240328 Date Completed: 20240329 Latest Revision: 20240330
رمز التحديث: 20240330
مُعرف محوري في PubMed: PMC10969995
DOI: 10.3390/ijms25063156
PMID: 38542130
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25063156