Induction of the myofibroblast phenotype following elastolytic injury to mouse lung.
The repair of alveolar structures following endotracheal administration of porcine pancreatic elastase (PPE) to mice involves the coordinated deposition of new matrix elements. We determined the induction of the myofibroblast phenotype following elastolytic injury to mouse lung by examining the expression of alpha-smooth muscle actin (alpha-SMA) by immunohistochemistry. We also examined elastin and alpha1(I) collagen mRNA expression by in situ hybridization. Changes in airspace dimensions were assessed by determining mean linear intercept. In untreated mice, alpha-SMA was localized to vascular structures and large airways, with no detectable expression in alveolar units. PPE induced alpha-SMA expression in damaged areas surrounding large vessels, in septal remnants, and in the opening ring of alveolar ducts. Elastin and alpha1(I) collagen mRNA expression were up-regulated in residual alveolar structures and septal walls. PPE dose-response studies indicated that alpha1(I) collagen and elastin mRNA expression were not induced in areas of normal lung adjacent to damaged lung. The administration of low dose PPE resulted in increased alpha-SMA protein and elastin mRNA expression in the cells comprising the opening ring of alveolar ducts. Our data suggest that repair mechanisms following elastolytic injury are confined to overtly damaged alveolar structures and involve the induction of the myofibroblast phenotype.
Rishikof
David C
DC
The Pulmonary Center, Boston University School of Medicine, 715 Albany Street, R-304, Boston, MA 02118, USA.
Lucey
Edgar C
EC
Kuang
Ping-Ping
PP
Snider
Gordon L
GL
Goldstein
Ronald H
RH
D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D004549:Elastin / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology*; D051379:Mice; D010196:Pancreatic Elastase / Q000494:pharmacology*; D010641:Phenotype; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine
D000199:Actins; D024042:Collagen Type I; D012333:RNA, Messenger; D004549:Elastin; D010196:Pancreatic Elastase