Pepsinogen C: a type 2 cell-specific protease

Abstract

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 surfactant protein-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.

Early Alveolar Epithelial Dysfunction Promotes Lung Inflammation in a Mouse Model of Hermansky-Pudlak Syndrome

“…Total cellular RNA from BAL cells and epithelial cells was isolated with an RNeasy kit (Qiagen, Valencia, CA) and a singleplex polymerase chain reaction (PCR) strategy using an ABI Prism 7900 system (ABI, Foster City, CA) as described previously (16). The primer/probe sets used were as follows: Ccl2 Mm00441242_m1, Nos2 Mm00440485_m1, IL-12b Mm00434174_m1, 18s Hs99999901_s1.…”

Airway Pepsin Levels in Otherwise Healthy Surgical Patients Receiving General Anesthesia With Endotracheal Intubation

“…A second important consideration is that, unlike pepsinogen A, pepsinogen C has been identifi ed in extragastric 36 sites, including the lungs. [37][38][39] Specifi cally, it appears to be expressed by type 2 pneumocytes and is involved in surfactant B processing. 40 As such, it is plausible that the detection of pepsin in the lower airways, if not specifi c for pepsin A, may be due to the detection of pepsinogen C in pathologic states in which surfactant B expression has been increased.…”

Pepsinogen C Proteolytic Processing of Surfactant Protein B

“…We have used this model previously in conjunction with adenovirus-mediated antisense SP-B expression and cysteine protease inhibitors to perturb SP-B expression (6,7). Naïve lung epithelial cells are devoid of mature SP-B protein and lamellar bodies and contain very low levels of SP-B RNA (21) and no pepsinogen C RNA or protein (17). This permitted us to study the onset of both SP-B expression and lamellar body genesis without background expression interfering with our ability to detect changes in proSP-B, mature SP-B, or intermediate forms of SP-B peptides.…”

“…Real-time RT-PCR reactions using a singleplex strategy were performed using an ABI Prism 7900 system (Applied Biosystems). The two-step PCR protocol was performed as detailed elsewhere (17). The following primer/ probe sets were used: SP-B Hs00167036_m1, pepsinogen C Hs00160052_m1, and GAPDH Hs99999905_m1, 18sHs99999901_ s1.…”

“…We recently described another aspartic protease, pepsinogen C, that is unique to alveolar type 2 cells in the lung (17). Pepsinogen C was highly induced during the process of in vivo and in vitro type 2 cell differentiation.…”