Background and Purpose: Primary cultures of lung epithelium provide ideal models tostudy the pathophysiology underlying airway and pulmonary diseases. However, manybronchiolar and alveolar epithelial cells gradually lose their phenotypic properties and fail tomaintain differentiated morphology and function under conventional culture conditions.Differential gene expression has been shown to be involved in many biological processesincluding cell differentiation. To understand the molecular mechanism involved in the loss ofdifferentiation, genes whose expression was modulated during in vitro culture of isolated ratlung epithelial cells were investigated. Methods: Suppression subtractive hybridization (SSH)takes advantage of subtractive hybridization and suppression PCR to detect differencesbetween cDNA populations. SSH was used to selectively amplify differentially expressedtranscripts which were enriched in freshly isolated compared to 4-day-cultured rat lungepithelial cells. The differential expression statuses of SSH-identified transcripts were furthervalidated by Northern blot analysis. The tissue distribution of differentially expressedtranscripts was also investigated by in situ hybridization and multiple tissue Northern blotanalysis. Results: A novel 0.6-kb transcript encoding a homolog of rat uteroglobin (UGRP1)was identified by SSH. The expression of UGRP1 mRNA was enriched in freshly isolated ratlung epithelial cells and diminished after 4 days of culture under conventional conditionsbased on Northern blot analysis. By in situ hybridization, transcripts of UGRP1 were detectedonly in bronchiolar epithelium and not in alveolar epithelium. UGRP1 mRNA waspredominantly distributed in the lung as compared to other tissues according to multipletissueNorthern blot analysis. Conclusions: Uteroglobin is a hormonally regulated secretoryprotein produced by the mucosal epithelia of various organs including the lung, uterus,prostate, and breast. Using SSH, we identified a novel uteroglobin homolog, UGRP1, whoseexpression was mainly detected in rat bronchiolar epithelial cells and was modulated duringin vitro culture. Further characterization of UGRP1 is needed to clarify its role in the regulationof bronchiolar epithelial cell function.