title: Nestin is a marker of lung remodeling secondary to myocardial infarction and type I diabetes in the rat.
abstract: Upregulation of the intermediate filament protein nestin was identified in a subpopulation of fibroblasts during reactive and reparative fibrosis and directly contributed to the enhanced proliferative phenotype. The present study tested the hypothesis that nestin was expressed in lung fibroblasts and the pattern of expression represented a distinct marker of pulmonary remodeling secondary to myocardial infarction and type I diabetes. Nestin((+)) fibroblasts were detected in rat lungs and a subpopulation exhibited a myofibroblast phenotype delineated by the co-expression of smooth muscle α-actin. In the lungs of myocardial infarcted rats, interstitial collagen content and nestin mRNA/protein levels were significantly increased despite the absence of secondary pulmonary hypertension, whereas smooth muscle α-actin protein expression was unchanged. Exposure of rat pulmonary fibroblasts to pro-fibrotic stimuli angiotensin II and transforming growth factor-β significantly increased nestin protein levels. In the lungs of type I diabetic rats, the absence of a reactive fibrotic response was associated with a significant downregulation of nestin mRNA/protein expression. Nestin was reported a target of miR-125b, albeit miR-125b levels were unchanged in pulmonary fibroblasts treated with pro-fibrotic stimuli. Nestin((+)) cells lacking smooth muscle α-actin/collagen staining were also identified in rodent lungs and a transgenic approach revealed that expression of the intermediate filament protein was driven by intron 2 of the nestin gene. The disparate regulation of nestin characterized a distinct pattern of pulmonary remodeling secondary to myocardial infarction and type I diabetes and upregulation of the intermediate filament protein in lung fibroblasts may have facilitated in part the reactive fibrotic response.
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada; Département de Physiologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Andréanne
authors.initials: A
authors.lastname: Chabot
authors.forename: Marc-Andre
authors.initials: MA
authors.lastname: Meus
authors.forename: Patrice
authors.initials: P
authors.lastname: Naud
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hertig
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Dupuis
authors.forename: Louis
authors.initials: L
authors.lastname: Villeneuve
authors.forename: Nabel
authors.initials: N
authors.lastname: El Khoury
authors.forename: Celine
authors.initials: C
authors.lastname: Fiset
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Jasmin
authors.forename: Angelino
authors.initials: A
authors.lastname: Calderone
mesh_terms: D000199:Actins / Q000096:biosynthesis; D056151:Airway Remodeling; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D024042:Collagen Type I / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism; D006333:Heart Failure / Q000473:pathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology*; D064231:Nestin / Q000096:biosynthesis* / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D000199:Actins; D000804:Angiotensin II; D015415:Biomarkers; D024042:Collagen Type I; D035683:MicroRNAs; D064231:Nestin; D012333:RNA, Messenger; D013311:Streptozocin; D016212:Transforming Growth Factor beta; C581261:MIRN125 microRNA, rat; C577486:Nes protein, rat; C498862:Acta2 protein, rat