Our previous results demonstrated that UGRP1 is expressed at very low levels in embryonic day (E) 12.5 of mouse embryos by RT-PCR, suggesting that UGRP1 may be involved in lung development. In fact, immunohistochemical study demonstrated that UGRP1 protein is expressed in the epithelial cells of E11.5 embryo lungs. In order to assess a possible role for UGRP1 during early embryonic lung development, early stages of fetal lungs from wild-type as well as T/EBP-null fetuses were subjected to ex vivo organ culture in the presence and absence of purified recombinant UGRP1. The organ culture study demonstrated that UGRP1 increases cell proliferation and facilitates branching morphogenesis of lung. T/EBP-heterozygous pregnant females carrying null fetuses were administered UGRP1 through the tail vein and fetal lungs subjected to histological and immunohistochemical analyses. After UGRP1 treatment, the epithelia of T/EBP-null embryo lungs, which consists of one to two layers of columnar epithelial cells covered with flattened epithelial and few ciliated cells, became comprised of stratified columnar cells with cilia, phenotypes normally found in wild-type mice, suggesting that UGRP1 promotes lung development in vivo.
In order to examine whether UGRP1 plays any role in late stages of embryonic lung development, UGRP1 was administered to pregnant wild-type females at the late gestational period and the preterm pups and/or their lungs were evaluated for extent of maturity using breathing motion, gross morphology and histology of lungs, expression of gestational stage-specific genes and phospholipid profiles. Based on these criteria, UGRP1-treated preterm pups demonstrated that their lungs have developed to the stage similar to term pups. All of these results taken together suggest that UGRP1 is a novel growth factor, promoting early as well as late stages of embryonic lung development. These results further suggest a potential clinical use of UGRP1 to treat preterm infants with problems associated with underdeveloped lungs.
Showing the most recent 10 out of 13 publications
