Nestin is a marker of lung remodeling secondary to myocardial infarction and type I diabetes in the rat

J Cell Physiol. 2015 Jan;230(1):170-9. doi: 10.1002/jcp.24696.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis
  • Airway Remodeling*
  • Angiotensin II / pharmacology
  • Animals
  • Biomarkers
  • Cell Differentiation
  • Collagen Type I / biosynthesis
  • Diabetes Mellitus, Type 1 / pathology*
  • Fibroblasts / metabolism
  • Heart Failure / pathology
  • Humans
  • Hypertension, Pulmonary / pathology
  • Hypertrophy, Right Ventricular / pathology
  • Lung / metabolism
  • Lung / pathology*
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • Myocardial Contraction / physiology
  • Myocardial Infarction / pathology*
  • Nestin / biosynthesis*
  • Nestin / genetics
  • Pulmonary Fibrosis / pathology
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • Transforming Growth Factor beta / pharmacology


  • Actins
  • Biomarkers
  • Collagen Type I
  • MIRN125 microRNA, rat
  • MicroRNAs
  • Nes protein, rat
  • Nestin
  • RNA, Messenger
  • Transforming Growth Factor beta
  • smooth muscle actin, rat
  • Angiotensin II
  • Streptozocin