Expression Of Proteins Of RA Signaling Pathway And JAK-STAT Pathway In Lung Tissue With Neonatal Respiratory Distress Syndrome And Their Significance

Neonatal respiratory distress syndrome(NRDS)is a severe disease which can lead to neonatal death. It has been known that it is caused by a deficiency of pulmonary surfactant (PS), especially its important ingredient——surfactant protein B (SP-B) which decreases lung compliance and functional residual capacity with increased dead space. Although premature infants are susceptible to NRDS because of the immaturity of alveolar typeⅡepithelial cells, not all premature infants suffered from NRDS, full-term newborns also suffered from NRDS, which suggests other mechanisms may be involved in pathophysiologic mechanism of this disease beside development. In addition, the detailed regulatory mechanism of SP-B has not been clearly elucidated yet. Pervious studies indicated that the transcription of SP-B gene is regulated by retinoic acid (RA) signaling pathway and Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, however, there has been no definite report whether the proteins in RA signaling pathway and JAK-STAT pathway abnormally express in NRDS. ObjectiveTo investigate the role of RA signaling pathway and JAK-STAT pathway in NRDS, the expression of retinoic acid receptorα(RARα),JAK1,STAT3 proteins were detected by immunohistochemical staining and the relationships between them and SP-B were analyzed.Methods30 cases of autopsy lung specimens were collected from neonates who succumbed to NRDS (NRDS group), and 20 cases of autopsy lung specimens were collected from neonates who succumbed to other diseases (control group). Then the following tests were undertaken: (1) HE staining of lung section to observe the morphological changes of the bronchi and alveolar epithelium in NRDS group and control group. (2) Immunohistochemical staining was used to detect the expression and distribution of SP-B,RARα,JAK1,STAT3 proteins in alveolar epithelial cells, the relationships between them and SP-B were studied.Results1.Morphology of lung tissue:Diffuse atelectasis of distal airspaces along with distension of distal airways is observed in the lung tissue of NRDS group. The homogeneous pink substances that lines the internal surface of dilated ductuli alveolares and respiratory bronchioles are hyaline membranes. In control group, most alveoli are patulous. The alveolar septa are widened. The alveolar spaces are filled with cuticular epithelium,meconium and exudation of serofluid and mononuclear macrophage.2.The immunohistochemical staining results are as the followings:①Compared with control group (0.3052±0.0847), the expression of SP-B was decreased in NRDS group (0.2468±0.0531, P<0.01).②In NRDS group, the expression of RARαwas mostly located in cytoplasm (22 / 30 cases); in control group, the expression of RARαwas mostly located in nuclei (10 / 20 cases). The distribution of RARαhad a significant difference between NRDS group and control group (P<0.05). The total expression of RARαin both nuclei and cytoplasm had no significant difference between NRDS group (0.3658±0.1469) and control group (0.4008±0.1681, P>0.05).③The expression of SP-B in the group with RARαexpression in nuclei was higher than that with RARαexpression in cytoplasm or RARαnegative expression (P<0.05).④The expressions of JAK1 and STAT3 in NRDS group (0.2560±0.0539 and 0.3486±0.0761, respectively) were lower than those in control group (0.2886±0.0539 and 0.4042±0.0661, P<0.05, respectively).⑤The result of correlation analysis indicated that the expression of RARαin all cases was positively correlated with the expression of SP-B (r=0.437,P<0.01).⑥No significant correlation was found between the expression of JAK1 and SP-B (P>0.05). There was no significant correlation between STAT3 and SP-B as well (P>0.05).Conclusion1.The abnormal distribution of RARαin cells may be responsible for the different expression of SP-B between NRDS group and control group, the expression of SP-B may be influenced by RARα, especially by its distribution in cells. The translocation of RARαfrom nucleus to cytoplasm may play an important role in the pathogenesis of NRDS.2.JAK-STAT pathway may be involved in the pathogenesis of NRDS.