Abstract:OBJECTIVE: Alveolar epithelium impairment is one of pathological changes associated with chronic lung disease (CLD). Hoxb5 is one of the few homeobox genes strongly expressed in the developing lung. This study investigated the expression of HoxB5, SPC and AQP5 in rats with CLD in order to explore the role of Hoxb-5 in impairment and reparation of alveolar epithelium. METHODS: Eighty neonatal rats were randomly exposed to hyperoxia (model group ) or to room air (control group) (n=40 each). The CLD model was induced by hyperoxia exposure. The expression of HoxB5, SPC and AQP5 protein and mRNA in the lung tissue was detected by immunohistochemistry and RT-PCR 1, 3, 7, 14 and 21 days after exposure. RESULTS: In the model group HoxB5 expression significantly decreased 7, 14 and 21 days after hyperoxia exposure. SPC expression decreased 3 days after hyperoxia exposure but increased significantly 7, 14 and 21 days after hyperoxia exposure as compared to the control group. AQP5 expression was progressively reduced with prolonged hyperoxia exposure. CONCLUSONS: Hyperoxia exposure may lead to alveolar epithelial cell (AEC) damage in neonatal rats. The increased SPC expression and decreased AQP5 expression suggested that the ability of differentiation and transformation of AECII into AECI decreased in neonatal rats with CLD. The decreased HoxB5 expression following hyperoxia exposure might contribute to a decreased ability of differentiation of AECII.[Chin J Contemp Pediatr, 2009, 11 (1):51-55]
[1]Gehring WJ, Affolter M, Bürglin T. Homeodomain proteins[J]. Annu Rev Biochem, 1994, 63:487-526.
[2]Manzanares M, Wada H, Itasaki N, Trainor PA, Krumlauf R, Holland PW. Conservation and elaboration of Hox gene regulation during evolution of the vertebrate head[J]. Nature, 2000, 408(6814):854-857.
[3]Golpon HA, Geraci MW, Moore MD, Miller HL, Miller GJ, Tuder RM, et al. HOX Genes in human lung:altered expression in primary pulmonary hypertension and emphysema[J].Am J Pathol, 2001, 158(3):955-966.
[4]Volpe MV, Martin A, Vosatka RJ, Mazzoni CL, Nielsen HC. Hoxb-5 expression in the developing mouse lung suggests a role in branching morphogenesis and epithelial cell fate[J]. Histochem Cell Biol, 1997, 108(6):495-504.
[5]Rottier R, Tibboel D. Fetal lung and diaphragm development in congenital diaphragmatic hernia[J]. Semin Perinatol, 2005, 29(2):86-93.
[6]Crapo JD, Barry BE, Gehr M. Cell number and cell characteristics of the normal human lung[J]. Am Rev Resp, 1982, 126(2):332-337.
[7]Lesur O, Arsalane K. Lung alveolar epithelial cell migration in vitro: modulators and regulation processes[J]. Am J Physiol, 1996, 370(3 Pt 1):311-319.
[8]Souza P, Tanswell AK, Post M. Different roles for PDGF-alpha and-beta receptors in embryonic lung development[J]. Am J Respir Cell Mol Biol, 1996, 15(4):551-562.
[9]Nielsen HC, Martin A, Volpe MV, Hutzis D, Vosatka RJ. Grow-th factor control of growth and epithelial differentiationin embryonic lungs[J]. Biochem Mol Med, 1997, 60(1):38-48.
[10]Zhao JJ, Lazzarini RA, Pick L. The mouse Hox 1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene[J]. Genes Dev, 1993, 7(3):343-354.
[11]Wu Q, Lothe RA, Ahlquist T, Silins I, Tropé CG, Micci F, et al. DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9,HOXB5,SCGB3A1,and CRABP1 as novel targets[J]. Molecular Cancer, 2007, 6:45.
[12]Hershko AY, Kafri1 T, Fainsod A, Razin A. Methylation of HoxA5 and HoxB5 and its relevance to expression during mouse development[J]. Gene, 2003, 302(1-2):65-72.