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1 Division of Neonatology, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Children's Hospital of Philadelphia, Philadelphia, PA, USA
2 Children's Hospital of Philadelphia, Philadelphia, PA, USA
* To whom correspondence should be addressed. E-mail: guttentag{at}email.chop.edu.
Pepsinogen C, also known as progastricsin or Pepsinogen II, is an aspartic protease expressed primarily in gastric chief cells. Prior microarray studies of an in vitro model of type 2 cell differentiation indicated that Pepsinogen C RNA was highly induced, comparable to surfactant protein RNA induction. Using second trimester human fetal lung, third trimester postnatal and adult lung and a model of type 2 cell differentiation, we examined the specificity of Pepsinogen C expression in lung. Pepsinogen C RNA and protein were only detected in > 22 wk gestation samples of neonatal lung or in adult lung tissue. By immunohistochemistry and in situ hybridization, Pepsinogen C expression was restricted to type 2 cells. Pepsinogen C expression was rapidly induced during type 2 cell differentiation and rapidly quenched with dedifferentiation of type 2 cells after withdrawal of hormones. In all samples, Pepsinogen C expression occurred concomitantly with or in advance of processing of SP-B to its mature 8 kDa form. Our results indicate that pepsinogen C is a type 2 cell specific marker that exhibits tight developmental regulation in vivo during human lung development, as well as during in vitro differentiation and dedifferentiation of type 2 cells.
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