Kalluri R, Gattone V H, Hudson B G
Department of Biochemistry/Molecular Biology and Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160, USA.
Connect Tissue Res. 1998;37(1-2):143-50. doi: 10.3109/03008209809028906.
Mutations in the genes encoding the alpha3(IV), alpha4(IV) and alpha5(IV) chains of type IV collagen have been implicated in the pathogenesis of Alport's syndrome, a hereditary disorder characterized by progressive nephropathy and sensorineural deafness. The known expression of these chains in kidney basement membranes supports the contention that they play a crucial role in the ultrafiltration function. Whether they play a role in auditory signal transduction remains unknown as heretofore, they have not been identified in the inner ear. In the present study, the expression of type IV collagen in cochlea of the inner ear of guinea pigs was determined. All six alpha-chains of type IV collagen were identified by biochemical and immunological methods. By indirect immunofluorescence, alpha1(IV) and alpha2(IV) chains were localized to the spiral limbus, basilar membrane and tectorial membrane. The alpha3(IV), alpha4(IV), alpha5(IV) and alpha6(IV) chains localized exclusively to the tectorial membrane and basilar membrane. These results suggest a possible role of type IV collagen chains in the active tuning of the basilar and tectorial membrane, an essential step in frequency discrimination and amplification of auditory signals.
编码IV型胶原α3(IV)、α4(IV)和α5(IV)链的基因突变与阿尔波特综合征的发病机制有关，阿尔波特综合征是一种遗传性疾病，其特征为进行性肾病和感音神经性耳聋。这些链在肾脏基底膜中的已知表达支持了它们在超滤功能中起关键作用的观点。它们是否在听觉信号转导中发挥作用仍然未知，因为迄今为止，它们尚未在内耳中被发现。在本研究中，测定了豚鼠内耳耳蜗中IV型胶原的表达。通过生化和免疫学方法鉴定了IV型胶原的所有六条α链。通过间接免疫荧光法，α1(IV)和α2(IV)链定位于螺旋缘、基底膜和盖膜。α3(IV)、α4(IV)、α5(IV)和α6(IV)链仅定位于盖膜和基底膜。这些结果表明IV型胶原链在基底膜和盖膜的主动调谐中可能发挥作用，这是听觉信号频率辨别和放大的一个重要步骤。
