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Lipocalin-2: A novel biomarker for lung hypoplasia in congenital diaphragmatic hernia fetus
( Yoshinori Moriyama ),( Hiroyuki Tsuda ),( Tomomi Kotani ),( Seiji Sumigama ),( Tomoko Nakano ),( Shima Hirako ),( Fumitaka Kikkawa ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-
Objective: Congenital diaphragmatic hernia (CDH) results in pulmonary hypoplasia and pulmonary hypertension, which are often fatal. In order to improve clinical care and counseling, reliable prenatal parameters predicting outcome of CDH fetus are urgently needed. Some prenatal predictors of outcome of CDH fetus have been reported, but they are focused mainly on the assessment of fetal lung volume, and a gold-standard parameter has not yet been established. The aim of this study is to establish an accurate predictive marker for fetal lung hypoplasia in CDH cases. Methods: Neonatal lung tissue was collected at E21 from normal and nitrofen-induced CDH rats (administered 100 mg orally at E9), and microarray analysis and real-time polymerase chain reaction (RT-PCR) were performed. Sixty-three human amniotic fluid samples of isolated CDH cases (n = 33) and scheduled Cesarean section (CS) without any fetal complication (controls) (n = 30) were obtained with signed informed consent. All amniotic fluid samples were obtained at CS performed at 35th to 38th weeks of gestation from April 2007 to January 2016. Results: Genes which showed significantly decreased expression in nitrofen-induced CDH lung were lipocalin-2 (9-fold) and GATA-2 (3.3-fold). In lipocalin-2, this result was confirmed by RT-PCR. Next, the lipocalin-2 level in human amniotic fluid was examined using ELISA, and it was significantly lower in CDH cases than in controls (73.7 ng/mL vs 163.8 ng/mL; p < 0.05). A significant positive correlation was observed between amniotic lipocalin- 2 level and lung area to head circumference ratio (p < 0.001, r<sup>2</sup> = 0.453). Conclusion: Our results suggest that gene expression level of lipocalin-2 was significantly decreased in hypoplastic lung in rats, and that amniotic lipocalin-2 level was significantly lower in CDH cases in human. Amniotic lipocalin- 2 can be a useful marker to predict the prognosis of fetal CDH.
CHOI, Young Ok,PARK, Jong-Ha,SONG, Young Sook,LEE, Wan,MORIYAMA, Yoshinori,CHOE, Han,LEEM, Chae Hun,JANG, Yeon Jin The Japan Endocrine Society 2007 Endocrine journal Vol.54 No.5
<P>In secretory cells, osmotic swelling of secretory granules is proposed to be an intermediate step in exocytic fusion of the granules with the plasma membrane. For osmotic swelling of the granule, a H <SUP>+</SUP> gradient generated by vacuolar-type H <SUP>+</SUP> -ATPase (V-ATPase) may be a driving force for accumulation of K <SUP>+</SUP> via its exchange with H <SUP>+</SUP> , concurrent with accumulation of Cl <SUP>-</SUP> and H<SUB>2</SUB>O. Here, we investigated whether a similar chemiosmotic mechanism is involved in the insulin-stimulated recruitment of GLUT4 to the plasma membrane in 3T3-F442A adipocytes. Incubating cells in a hypo-osmotic medium significantly increased 2-deoxy glucose (2-DG) uptake and the plasma membrane GLUT4 content (possibly via induction of osmotic swelling of GLUT4-containing vesicles (G4V)) and also potentiated the insulin-stimulated 2-DG uptake. Promotion of the G4V membrane ionic permeability using nigericin, an electroneutral K <SUP>+</SUP> /H <SUP>+</SUP> exchange ionophore, increased 2-DG uptake and the plasma membrane GLUT4 content. However, co-treatment with nigericin and insulin did not show an additive effect. Bafilomycin A<SUB>1</SUB>, a diagnostically specific inhibitor of V-ATPase, inhibited insulin- and nigericin-stimulated 2-DG uptake. Immunoadsorption plus immunoblotting demonstrated that GLUT4 and V-ATPase co-localize in the same intracellular membranes. Together, these results indicate that V-ATPases in the G4V membrane may play an important role in the insulin-stimulated exocytic fusion of G4V with the plasma membrane via its participation in osmotic swelling of the vesicle.</P>