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Identification of Genes Differentially Expressed in Rat Alveolar Type I Cells

Departments of Medicine, Pediatrics, and Cardiovascular Research Institute, University of California San Francisco, San Francisco; and the David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California

Address correspondence to: Leland G. Dobbs, M.D., Suite 150, 3333 California St., San Francisco, CA 94118. Email: dobbs{at}itsa.ucsf.edu

Although 98% of the internal surface area of the lung is lined by alveolar type I cells, little is known about the functions of this cell type. Using freshly isolated rat type I and type II cells, we created a subtraction library by suppression subtractive hybridization to identify genes differentially expressed by type I cells. We identified twelve genes of known function that are differentially expressed by type I cells. Differential expression of all 12 genes was confirmed by Northern blotting; we confirmed differential expression by immunocytochemistry for 3 genes for which suitable antibodies were available. Most of the genes code for proteins that are multifunctional. From the known functions of these genes, we infer that type I cells may play a role in the maintenance of normal alveolar homeostasis and protection from injury, lung development and remodeling, host defense, tumor/growth suppression, and surfactant metabolism, among other functions.

Abbreviations: alveolar macrophage, AM • annexin VIII, ANXA8 • crystallin B, CRYAB • epithelial membrane protein 2, EMP2 • epithelial sodium channel, ENaC • inducible nitric oxide synthase, iNOS • c-Jun N-terminal kinases, JNK • mitogen-activated protein kinase, MAPK • matrix metalloproteinase, MMP • group IIA secretory phospholipase A2, sPLA2-IIA • protein kinase C alpha, PKC • phosphatidylserine, PS • receptor for advanced glycation end products, RAGE • semaphorin 3F, Sema3F • serum deprivation response protein, SDPR • suppression subtractive hybridization, SSH • tissue inhibitor of metalloproteinase 3, TIMP3 • topoisomerase III alpha, TOP3A • tumor suppressor of lung cancer 1, TSLC1 • vascular endothelial growth factor, VEGF

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