Mitochondrial biogenesis in the pulmonary vasculature during inhalational lung injury and fibrosis.
Cell survival and injury repair is facilitated by mitochondrial biogenesis; however, the role of this process in lung repair is unknown. We evaluated mitochondrial biogenesis in the mouse lung in two injuries that cause acute inflammation and in two that cause chronic inflammation and pulmonary fibrosis. By using reporter mice that express green fluorescent protein (GFP) exclusively in mitochondria, we tracked mitochondrial biogenesis and correlated it with histologic lung injury, proliferation, and fibrosis. At 72 hours after acute LPS or continuous exposure to hyperoxia (Fio2, 1.0), the lungs showed diffuse infiltration by inflammatory cells in the alveolar region. In reporter mice, patchy new mitochondrial fluorescence was found in the alveolar region but was most prominent and unexpected in perivascular regions. At 14 days after instillation of asbestos or bleomycin, diffuse chronic inflammation had developed, and green fluorescence appeared in inflammatory cells in the expanded interstitium and was most intense in smooth muscle cells of pulmonary vessels. In all four lung injuries, mitochondrial fluorescence colocalized with mitochondrial superoxide dismutase, but not with proliferating cell nuclear antigen. These data indicate that vascular mitochondrial biogenesis is activated in diverse inhalational lung injuries along with oxidative stress. This finding indicates a unique and unexpected mechanism of metabolic adaptation to pulmonary fibrotic injuries.
Carraway
Martha S
MS
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. carr001@mc.duke.edu
Suliman
Hagir B
HB
Kliment
Corrine
C
Welty-Wolf
Karen E
KE
Oury
Tim D
TD
Piantadosi
Claude A
CA
D000818:Animals; D001194:Asbestos / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D004195:Disease Models, Animal; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000378:metabolism
D001761:Bleomycin; D001194:Asbestos; D013482:Superoxide Dismutase