Rabbit Anti-Human IHH (a.a. 10-317) Polyclonal antibody

Chronic intermittent hypoxia and hedgehog (Hh) pathway dysregulation are associated with nonalcoholic fatty liver disease (NAFLD) progression. In this study, we determined the relationship between obstructive sleep apnea (OSA)/nocturnal hypoxia and Hh signaling in pediatric NAFLD. Adolescents with histologic NAFLD (n=31) underwent polysomnogram testing, laboratory testing, and Sonic Hh (SHh), Indian hedgehog (IHh), glioblastoma-associated oncogene 2 (Gli2), keratin 7 (K7), alpha-smooth muscle actin (-SMA), and hypoxia-inducible factor 1 (HIF-1) immunohistochemistry. Aspartate aminotransferase (AST) correlated with SHh, r=0.64; Gli2, r=0.4; alpha-SMA, r=0.55; and K7, r=0.45 (P<0.01), as did alanine aminotransferase (ALT) (SHh, r=0.51; Gli2, r=0.43; alpha-SMA, r=0.51; P<0.02). SHh correlated with NAFLD activity score (r=0.39), whereas IHh correlated with inflammation (r=-0.478) and histologic grade (r=-0.43); P<0.03. Subjects with OSA/hypoxia had higher SHh (4.0 +/- 2.9 versus 2.0 +/- 1.5), Gli2 (74.2 +/- 28.0 versus 55.8 +/- 11.8), and alpha-SMA (6.2 +/- 3.3 versus 4.3 +/- 1.2); compared to those without (P<0.03). OSA severity correlated with SHh (r=0.31; P=0.09) and Gli2 (r=0.37; P=0.04) as did hypoxia severity, which was associated with increasing SHh (r=-0.53), Gli2 (r=-0.52), -SMA (r=-0.61), and K7 (r=-0.42); P<0.02. Prolonged O-2 desaturations <90% also correlated with SHh (r=0.55) and Gli2 (r=0.61); P<0.05. Conclusion: The Hh pathway is activated in pediatric patients with NAFLD with nocturnal hypoxia and relates to disease severity. Tissue hypoxia may allow for functional activation of HIF-1, with induction of genes important in epithelial-mesenchymal transition, including SHh, and NAFLD progression.

Orexin neuropeptides (OxA and OxB) and their receptors (OX1R and OX2R) are involved in maintenance of sleep and wakefulness, and are regulated by various environmental stimuli. We studied piglets, in the early neonatal period, exposed to 48-min of intermittent hypercapnic hypoxia (IHH; 7% O-2/8% CO2) alternating with air. Three groups of 13-14 day-old piglets with IHH exposure of 1-day (1D-IHH)(n = 7), 2-days (2D-IHH) (n = 7) and 4-days (4D-IHH) (n = 8) were compared to controls (exposed only to air, n = 8). Immunoreactivity of OxA and OxB was studied in the piglet hypothalamic regions of the dorsomedial hypothalamus (DMH), perifornical area (PeF) and lateral hypothalamic area (LH). Results showed that after 1D- and 2D-IHH, total OxA and OxB expression decreased by 20% (p <= 0.005) and 40% (p < 0.001), respectively. After 4D-IHH, the decrease in OxA and OxB was 50% (p < 0.001). These findings indicate that a chronic IHH exposure induces greater changes in orexin neuropeptide expression than an acute 1-day exposure in the hypothalamus. This may be causally related to the dysregulation of sleep. (C) 2015 Elsevier Ltd. All rights reserved.