title: Transcriptional changes in adhesion-related genes are site-specific during noise-induced cochlear pathogenesis.
abstract: Cell-cell junctions and junctions between cells and extracellular matrix are essential for maintenance of the structural and functional integrity of the cochlea, and are also a major target of acoustic trauma. While morphological assessments have revealed adhesion dysfunction in noise-traumatized cochleae, the molecular mechanisms responsible for adhesion disruption are not clear. Here, we screened the transcriptional expression of 49 adhesion-related genes in normal rat cochleae and measured the expression changes in the early phases of cochlear pathogenesis after acoustic trauma. We found that genes from four adhesion families, including the immunoglobulin superfamily and the integrin, cadherin, and selectin families, are expressed in the normal cochlea. Exposure to an intense noise at 120dB sound pressure level (SPL) for 2h caused site-specific changes in expression levels in the apical and the basal sections of the sensory epithelium. Expression changes that occurred in the cochlear sensory epithelium were biphasic, with early upregulation at 2h post-noise exposure and subsequent downregulation at 1day post-exposure. Importantly, the altered expression level of seven genes (Sgce, Sell, Itga5, Itgal, Selp, Cntn1 and Col5a1) is related to the level of threshold shift of the auditory brainstem response (ABR), an index reflecting functional change in the cochlea. Notably, the genes showing expression changes exhibited diverse constitutive expression levels and belong to multiple adhesion gene families. The finding of expression changes in multiple families of adhesion genes in a temporal fashion (2h vs. 1day) and a spatial fashion (the apical and the basal sensory epithelia as well as the lateral wall tissue) suggests that acoustic overstimulation provokes a complex response in adhesion genes, which likely involves multiple adhesion-related signaling pathways.
authors: Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA. qcai@buffalo.edu
authors: Qunfeng
authors: Q
authors: Cai
authors: Minal
authors: M
authors: Patel
authors: Donald
authors: D
authors: Coling
authors: Bo Hua
authors: BH
authors: Hu
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D003051:Cochlea / Q000378:metabolism / Q000503:physiopathology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D020869:Gene Expression Profiling; D006317:Hearing Loss, Noise-Induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D009622:Noise / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D015815:Cell Adhesion Molecules