Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings
Δημιουργός/Συγγραφέας:	Sfikakis, Petros P Vlachogiannis, Nikolaos I Ntouros, Panagiotis A Mavrogeni, Sophie Maris, Thomas G Karantanas, Apostolos H [EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L.
Ημερομηνία:	2022-03-16
Γλώσσα:	Αγγλικά
ISSN:	2075-1729
DOI:	10.3390/life12030430
Άλλο:	35330181
Περίληψη:	Microvascular wall abnormalities demonstrated by nailfold capillaroscopy in systemic sclerosis (SSc) may result in microhemorrhagic deposition of erythrocyte-derived iron. Such abnormalities precede fibrosis, which is orchestrated by myofibroblasts. Iron induces endothelial-to-mesenchymal transition in vitro, which is reversed by reactive oxygen species (ROS) scavengers. The conversion of quiescent fibroblasts into profibrotic myofibroblasts has also been associated with ROS-mediated activation of TGF-β1. Given that iron overload predisposes to ROS formation, we hypothesized that the uptake of erythrocyte-derived iron by resident cells promotes fibrosis. Firstly, we show that iron induces oxidative stress in skin-derived and synovial fibroblasts in vitro, as well as in blood mononuclear cells ex vivo. The biological relevance of increased oxidative stress was confirmed by showing the concomitant induction of DNA damage in these cell types. Similar results were obtained in vivo, following intravenous iron administration. Secondly, using magnetic resonance imaging we show an increased iron deposition in the fingers of a patient with early SSc and nailfold microhemorrhages. While a systematic magnetic resonance study to examine tissue iron levels in SSc, including internal organs, is underway, herein we propose that iron may be a pathogenetic link between microvasculopathy and fibrosis and an additional mechanism responsible for increased oxidative stress in SSc.
Τίτλος πηγής δημοσίευσης:	Life (Basel, Switzerland)
Τόμος/Κεφάλαιο:	12
Τεύχος:	3
Θεματική Κατηγορία:	[EL] Παθολογία[EN] Pathology [EL] Βιοχημεία[EN] Biochemistry [EL] Φασματοσκοπία[EN] Spectroscopy [EL] Κυτταρολογία[EN] Cytology
Λέξεις-Κλειδιά:	MR imaging/quantification Fibrosis Iron deposition Oxidative stress Systemic sclerosis Vasculopathy
EU Grant identifier:	ELKE-NKUA #0974
Κάτοχος πνευματικών δικαιωμάτων:	© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.mdpi.com/2075-1729/12/3/430
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο