Postpneumonectomy lung growth: a model of reinitiation of tropoelastin and type I collagen production in a normal pattern in adult rat lung.
Elastic and collagen fibers confer recoil and tensile strength on the pulmonary vasculature, airways, alveolar walls, and pleura. These durable extracellular matrix components are primarily synthesized during lung development and growth, and are expressed at very low levels in healthy adult lung. However, reinitiation of elastin and collagen synthesis in diseases of adult lung, such as idiopathic pulmonary fibrosis, often leads to excessive or aberrant deposition of elastin and collagen which contribute to the pathophysiology of these diseases. We used an experimental model of postpneumonectomy lung growth to determine whether normal patterns of synthesis and deposition of these critical structural components can occur in the adult lung. Male Sprague-Dawley rats (250-300 grams) were subjected to left pneumonectomy and right lobectomy. The remaining lung tissue was harvested for analysis after 3, 7, or 14 days. Compensatory growth of the remaining right lung progressed throughout the time course. Total desmosine and hydroxyproline content increased in the postpneumonectomy lung, reflecting increased elastin and collagen accumulation, but both were normal in content per weight of lung tissue. Northern analysis demonstrated induction of tropoelastin and type I procollagen mRNA expression in lungs of pneumonectomy rats. In situ hybridization localized tropoelastin and type I procollagen mRNA expression to anatomical sites similar to those seen during lung development. These data indicate that the adult lung can reinitiate elastin and collagen production and deposit these extracellular matrix components in a normal pattern.
Koh
D W
DW
Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
Roby
J D
JD
Starcher
B
B
Senior
R M
RM
Pierce
R A
RA
D000818:Animals; D000831:Animals, Newborn; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000032:analysis; D003895:Desmosine / Q000378:metabolism; D005786:Gene Expression Regulation; D006909:Hydroxyproline / Q000096:biosynthesis; D008168:Lung / Q000737:chemistry / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D011013:Pneumonectomy; D011347:Procollagen / Q000235:genetics; D011650:Pulmonary Alveoli / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014333:Tropoelastin / Q000096:biosynthesis* / Q000235:genetics
D011347:Procollagen; D012333:RNA, Messenger; D014333:Tropoelastin; D003895:Desmosine; D003094:Collagen; D004247:DNA; D006909:Hydroxyproline