J Tesfaigzi, J Th'ng, JA Hotchkiss, JR Harkema and PS Wright
Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185, USA.

Small proline-rich proteins, believed to be precursor proteins for the crosslinked envelope formation in cells undergoing squamous differentiation, are encoded by the SPRR genes. To further investigate the role of these proteins, the time course of increased synthesis of SPRR1 mRNA in nasal epithelia of rats exposed to cigarette smoke was determined, and the deduced amino acid sequence of the rat SPRR1 was compared with those of other species. Using the pig homologue (20K) antisense cRNA probe, high levels of SPRR1 transcript were detected by in situ hybridization in squamous epithelia that line the nasal vestibule and hard palate of the rat. Basal cells of both the vestibule and palate contained low levels of the transcript, and increasing amounts were detected in the squamous layers. In rats exposed to 250 mg/m3 (total particulate matter) cigarette smoke 6 h/day for 5 days, the number of small mucous cells increased in the respiratory epithelium of the nasal septum in the early stages of squamous differentiation, but were gradually replaced by squamous metaplastic cells. During this transition, hybridization of the 20K antisense cRNA probe increased in the epithelial and mesenchymal cells, indicating that SPRR1 protein could have roles in cellular differentiation other than as a building block of the crosslinked envelope. Similarly, high levels of SPRR1 transcript were detected in the nasal transitional epithelium lining internal walls and maxilloturbinates that had undergone squamous metaplasia after cigarette smoke exposure. At 5 days after the withdrawal of cigarette smoke exposure, the morphology of the midseptal epithelium returned to that of a pseudostratified mucociliary epithelium and the epithelia lining the maxilloturbinates to that of a transitional epithelium. Accompanying this change in morphology of the tissues, the levels of SPRR1 transcripts significantly decreased in the epithelia. However, in the mesenchyme no significant decrease was observed during this recovery. RNA prepared from the external nose surrounding the nasal vestibule contained a transcript of about 0.9 kb that hybridized to the 20K cDNA probe on Northern blot analysis. DNA sequence analysis of the transcript confirmed the identity as that of the SPRR mRNA with its characteristic repeat encoding the oligopeptide with the general consensus -EPC*PKVP-. However, the rat homologue rSPRR1 contained more repeats of the oligopeptide compared with those of higher mammals such as the rabbit, pig, and human, suggesting a possible inverse relation between number of repeats and evolution development. This finding suggests that the number of repeats in the protein may be redundant; however, the conserved sequence of the peptide indicates that this region is essential for the function of this protein.

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