December 13, 2006; doi:10.1152/ajpcell.00588.2005.-The aquaporin (AQP)2 channel mediates the reabsorption of water in renal collecting ducts in response to arginine vasopressin (AVP) and hypertonicity. Here we show that AQP2 expression is induced not only by the tonicityresponsive enhancer binding protein (TonEBP)/nuclear factor of activated T cells (NFAT)5-mediated hypertonic stress response but also by the calcium-dependent calcineurin-NFATc pathway. The induction of AQP2 expression by the calcineurin-NFATc pathway can occur in the absence of TonEBP/NFAT5. Mutational and chromatin immunoprecipitation analyses revealed the existence of functional NFAT binding sites within the proximal AQP2 promoter responsible for regulation of AQP2 by NFATc proteins and TonEBP/NFAT5. Contrary to the notion that TonEBP/NFAT5 is the only Rel/NFAT family member regulated by tonicity, we found that hypertonicity promotes the nuclear translocation of NFATc proteins for the subsequent induction of AQP2 expression. Calcineurin activity was also found to be involved in the induction of TonEBP/NFAT5 expression by hypertonicity, thus further defining the signaling mechanisms that underlie the TonEBP/NFAT5 osmotic stress response pathway. The coordinate regulation of AQP2 expression by both osmotic stress and calcium signaling appears to provide a means to integrate diverse extracellular signals into optimal cellular responses. aquaporin; nuclear factor of activated T cells; tonicity-responsive enhancer binding protein; osmotic response CELLS OF THE RENAL MEDULLA exist in a unique tissue environment characterized by extremes of hypertonicity during periods of antidiuresis, which allows for the efficient reabsorption of water from the glomerular filtrate (3). The hypertonic interstitial environment allows water to diffuse through the tubular epithelial cell membrane via aquaporin (AQP) water channels. Genetic studies in both mice and humans indicate that multiple AQPs, including AQP2, play a critical role in water transport in the kidney (21). AQP2 is expressed in cells of the renal collecting ducts that are exposed to the potentially hypertonic environment. Binding of arginine vasopressin (AVP) to AVP receptor 2 (AVPR2) induces the translocation of AQP2 from storage vesicles to the plasma membrane (21). Mutations in components of this pathway, especially in AVPR2 and AQP2, cause defects in urine concentration manifested as nephrogenic diabetes insipidus (NDI) (23). While AVP/AVPR2 signaling can regulate the long-term expression of AQP2 (35), regulation of AQP2 by AVP-independent mechanisms has also been reported (14,20,42).Although the hypertonic environment within the kidney allows for reabsorption of water, it also subjects cells to a potentially lethal osmotic stress. The cellular response that permits cells of the renal medulla to adapt and survive within a hypertonic environment is mediated by the tonicity-responsive enhancer binding protein (TonEBP)/nuclear factor of activated T cells (NFAT)5 transcription factor (13). TonEBP/ NF...
Objective: To identify postnatal risk factors for bronchopulmonary dysplasia (BPD) development in preterm infants with gestational age ≤32 weeks. Methods: Seventy-two preterm infants(30 with BPD and 42 non-BPD controls) admitted in the neonatal intensive care unit (NICU) of the Children's Hospital of Soochow University during 2017 were enrolled in this prospective longitudinal study. Perinatal clinical data, a neonatal critical illness score (NCIS), different soluble B7-H3(sB7-H3), and interleukin-18 (IL-18) levels by days after birth were collected. An early predictive model for BPD development was established based on clinical data using multiple logistic regression analysis. And the sensitivity and specificity of the model were assesed by ROC curve. Results: Electrolyte disturbances, hemodynamically significant patent ductus arteriosus (hs-PDA), and the age that infants achieved 120 kcal/kg.d via enteral feeding ≥40 days after birth were found to be associated with the BPD pathogenesis. Serum sB7-H3, IL-18, and NCIS were significantly higher in the BPD group compared to the non-BPD group (p < 0.05). BPD group had significantly lower enteral fluid and caloric intake compared to the non-BPD group at 1, 7, 14, and 28 days after birth. The risk factors were analyzed by multiple logistic regression and a predictive model of a combination of sB7-H3 (day 7), IL-18 (day 14), NCIS, and clinical risk factors was evaluated via ROC curve with an area under the curve (AUC) of 0.960 having sensitivity of 86.7% and a specificity of 97.6%, respectively. Conclusion: The causes of BPD are multifactorial postnatal risk factors. And the combination of sB7-H3 (day 7), IL-18 (day 14), NCIS, and clinical risk factors (electrolyte disturbances, hs-PDA, and the age that infants achieved 120 kcal/kg.d via enteral feeding ≥40 days after birth) might be served as an optimal predictive model for the occurrence of BPD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.