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Prevention of In Utero Nicotine‐Induced Bone Marrow Mesenchymal Stem Cell (BMMSC) Myofibroblast Differentation by Augmenting Lipofibroblast Phenotype
Author(s) -
Rehan Virender K.,
Guo Pinzheng,
Cruz Emmanuel,
Chap Kimberley,
Lee WaiNang Paul,
Torday John S.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.753.6
Subject(s) - transdifferentiation , nicotine , in utero , endocrinology , medicine , dapi , chemistry , pharmacology , biology , fetus , pathology , pregnancy , staining , cell , biochemistry , genetics
Alveolar lipofibroblasts (LIFs) are critical for lung homeostasis and injury/repair. We have shown that in utero nicotine exposure drives the differentiation of LIFs to myofibroblasts (MYFs). Whether BMMSCs can be preferentially driven to LIF phenotype is not known. We hypothesized that PPARγ agonists can prevent in utero nicotine‐induced MYF differentiation of BMMSCs and drive these cells to a LIF phenotype. Sprague Dawley dams were given 1 mg/kg nicotine from day 3 of pregnancy until term. After spontaneous delivery, pups were given either 1 or 3 mg/kg RGZ or saline (control) from postnatal day 1 to 3 weeks, when pups were sacrificed and BMMSCs were isolated and characterized for morphologic, molecular, and functional characteristics by Oil Red O staining, Western blotting, RT‐PCR, triolein uptake, and 1,2‐ 13 C‐glucose labeling. In utero nicotine exposure resulted in decreased Oil Red O staining, triolein uptake, oxidative/non‐oxidative ribose synthesis, PPARγ expression by BMMSCs, but markedly increased α‐SMA expression; all features, suggestive of in utero nicotine‐induced LIF‐to‐MYF transdifferentiation. Concomitant treatment with RGZ virtually blocked all of these nicotine‐induced morphologic, molecular, and functional changes, suggesting a possible targeted molecular preventive and/or therapeutic approach to prevent in utero nicotine‐induced lung injury (TRDRP 17R0170).