Vol. 276, Issue 6, L1027-L1036, June 1999
A novel developmentally regulated gene in lung mesenchyme:
homology to a tumor-derived trypsin inhibitor
Feige
Kaplan1,2,3,
Pierre
Ledoux1,2,
Ferhat Q.
Kassamali1,2,
Stéphane
Gagnon4,
Martin
Post4,5,
David
Koehler4,
Julie
Deimling4, and
Neil B.
Sweezey4,5
1 McGill University-Montreal
Children's Hospital Research Institute, Montreal, Quebec H3H 1P3;
2 Department of Human Genetics and
3 Department of Pediatrics,
McGill University, Montreal, Quebec H3H 1B1;
4 Lung Biology Research,
Research Institute, The Hospital for Sick Children, Toronto, Ontario
M5G 1X8; and 5 Departments of
Paediatrics and Physiology, University of Toronto, Toronto, Ontario,
Canada M5S 1A8
We used differential display-PCR (DD-PCR) to
identify glucocorticoid-inducible genes that regulate lung development
in late gestation. DD-PCR, a method to screen for differentially
expressed genes, is based on a comparison of mRNAs isolated from a
subset of two or more cell populations by analysis of RT-PCR products on DNA-sequencing gels. We isolated cDNA probes representing mRNAs expressed in primary cultures of rat lung fibroblasts, but not in
epithelial cells, on fetal day 20. A
day 20 glucocorticoid-treated fibroblast cDNA library was screened with a single probe to isolate the
3.1-kb cDNA late-gestation lung 1 (LGL1; GenBank accession no. AF109674) encoding a deduced polypeptide of 188 amino acids. Northern analysis confirmed that LGL1
is expressed in human, rat, and mouse fetal lungs, induced by
glucocorticoid, developmentally regulated in fibroblasts but not
detectable in epithelium. In situ hybridization confirmed
LGL1 expression in the mesenchyme, but
not in the epithelium, of fetal rat lung, kidney, and gut. The
predicted LGL1 gene product (lgl1)
showed 81% homology to P25TI, a polypeptide trypsin inhibitor recently
identified in human glioblastoma and neuroblastoma cells but not
detected in normal human tissues. Both lgl1 and P25TI belong to the
CRISP family of cysteine-rich extracellular proteins. Trypsin is
produced by both normal bronchial epithelial and lung adenocarcinoma
cells. Although additional studies will be necessary to clearly
establish a functional role for lgl1, we propose that lgl1 has a role
in normal lung development that is likely to be via regulation of extracellular matrix degradation.
genes in lung development; mesenchymal-epithelial signaling
