Prevention of Perinatal Nicotine-induced Bone Marrow Mesenchymal Stem Cell Myofibroblast Differentiation by Augmenting the Lipofibroblast Phenotype

Perinatal nicotine exposure drives the differentiation of alveolar lipofibroblasts (LIFs), which are critical for lung injury repair, to myofibroblasts (MYFs), which are the hallmark of chronic lung disease. Bone marrow-derived mesenchymal stem cells (BMSCs) are important players in lung injury repair; however, how these cells are affected with perinatal nicotine exposure and whether these can be preferentially driven to a lipofibroblastic phenotype are not known. We hypothesized that perinatal nicotine exposure would block offspring BMSCs lipogenic differentiation, driving these cells towards a MYF phenotype. Since PPAR agonists can prevent nicotine-induced MYF differentiation of LIFs, we further hypothesized that modulation of PPAR expression would inhibit nicotine's myogenic effect on BMSCs. Sprague Dawley dams were perinatally administered nicotine (1 mg/kg bodyweight) with or without the potent PPAR agonist rosiglitazone (RGZ), both administered subcutaneously. At postnatal day 21, BMSCs were isolated and characterized morphologically, molecularly, and functionally for their lipogenic and myogenic potentials. Perinatal nicotine exposure resulted in decreased oil red O staining, triolein uptake, expression of PPAR and its downstream target gene ADRP by BMSCs, but enhanced αSMA and fibronectin expression, and activated Wnt signaling, all features indicative of their inhibited lipogenic, but enhanced myogenic potential. Importantly, concomitant treatment with RGZ virt...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research