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The emerging importance of immunophilins in fibrosis development

Immunophilins are a family of proteins encompassing FK506-binding proteins (FKBPs) and cyclophilins (Cyps). FKBPs and Cyps exert peptidyl-prolyl cis-trans isomerase (PPIase) activity, which facilitates diverse protein folding assembly, or disassembly. In addition, they bind to immunosuppressant medi...

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Autores principales: Alqudah, Abdelrahim, AbuDalo, Rawan, Qnais, Esam, Wedyan, Mohammed, Oqal, Muna, McClements, Lana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164022/
https://www.ncbi.nlm.nih.gov/pubmed/36302992
http://dx.doi.org/10.1007/s11010-022-04591-1
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author Alqudah, Abdelrahim
AbuDalo, Rawan
Qnais, Esam
Wedyan, Mohammed
Oqal, Muna
McClements, Lana
author_facet Alqudah, Abdelrahim
AbuDalo, Rawan
Qnais, Esam
Wedyan, Mohammed
Oqal, Muna
McClements, Lana
author_sort Alqudah, Abdelrahim
collection PubMed
description Immunophilins are a family of proteins encompassing FK506-binding proteins (FKBPs) and cyclophilins (Cyps). FKBPs and Cyps exert peptidyl-prolyl cis-trans isomerase (PPIase) activity, which facilitates diverse protein folding assembly, or disassembly. In addition, they bind to immunosuppressant medications where FKBPs bind to tacrolimus (FK506) and rapamycin, whereas cyclophilins bind to cyclosporin. Some large immunophilins have domains other than PPIase referred to as tetratricopeptide (TPR) domain, which is involved in heat shock protein 90 (Hsp90) and heat shock protein 70 (Hsp 70) chaperone interaction. The TPR domain confers immunophilins’ pleotropic actions to mediate various physiological and biochemical processes. So far, immunophilins have been implicated to play an important role in pathophysiology of inflammation, cancer and neurodegenerative disorders. However, their importance in the development of fibrosis has not yet been elucidated. In this review we focus on the pivotal functional and mechanistic roles of different immunophilins in fibrosis establishment affecting various organs. The vast majority of the studies reported that cyclophilin A, FKBP12 and FKBP10 likely induce organ fibrosis through the calcineurin or TGF-β pathways. FKBP51 demonstrated a role in myelofibrosis development through calcineurin-dependant pathway, STAT5 or NF-κB pathways. Inhibition of these specific immunophilins has been shown to decrease the extent of fibrosis suggesting that immunophilins could be a novel promising therapeutic target to prevent or reverse fibrosis.
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spelling pubmed-101640222023-05-08 The emerging importance of immunophilins in fibrosis development Alqudah, Abdelrahim AbuDalo, Rawan Qnais, Esam Wedyan, Mohammed Oqal, Muna McClements, Lana Mol Cell Biochem Article Immunophilins are a family of proteins encompassing FK506-binding proteins (FKBPs) and cyclophilins (Cyps). FKBPs and Cyps exert peptidyl-prolyl cis-trans isomerase (PPIase) activity, which facilitates diverse protein folding assembly, or disassembly. In addition, they bind to immunosuppressant medications where FKBPs bind to tacrolimus (FK506) and rapamycin, whereas cyclophilins bind to cyclosporin. Some large immunophilins have domains other than PPIase referred to as tetratricopeptide (TPR) domain, which is involved in heat shock protein 90 (Hsp90) and heat shock protein 70 (Hsp 70) chaperone interaction. The TPR domain confers immunophilins’ pleotropic actions to mediate various physiological and biochemical processes. So far, immunophilins have been implicated to play an important role in pathophysiology of inflammation, cancer and neurodegenerative disorders. However, their importance in the development of fibrosis has not yet been elucidated. In this review we focus on the pivotal functional and mechanistic roles of different immunophilins in fibrosis establishment affecting various organs. The vast majority of the studies reported that cyclophilin A, FKBP12 and FKBP10 likely induce organ fibrosis through the calcineurin or TGF-β pathways. FKBP51 demonstrated a role in myelofibrosis development through calcineurin-dependant pathway, STAT5 or NF-κB pathways. Inhibition of these specific immunophilins has been shown to decrease the extent of fibrosis suggesting that immunophilins could be a novel promising therapeutic target to prevent or reverse fibrosis. Springer US 2022-10-27 2023 /pmc/articles/PMC10164022/ /pubmed/36302992 http://dx.doi.org/10.1007/s11010-022-04591-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Alqudah, Abdelrahim
AbuDalo, Rawan
Qnais, Esam
Wedyan, Mohammed
Oqal, Muna
McClements, Lana
The emerging importance of immunophilins in fibrosis development
title The emerging importance of immunophilins in fibrosis development
title_full The emerging importance of immunophilins in fibrosis development
title_fullStr The emerging importance of immunophilins in fibrosis development
title_full_unstemmed The emerging importance of immunophilins in fibrosis development
title_short The emerging importance of immunophilins in fibrosis development
title_sort emerging importance of immunophilins in fibrosis development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164022/
https://www.ncbi.nlm.nih.gov/pubmed/36302992
http://dx.doi.org/10.1007/s11010-022-04591-1
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