Liu Ziyi, Bai Xinfeng, Wan Peifeng, Mo Fan, Chen Ge, Zhang Jian, Gao Jiangang
School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, China.
Front Cell Dev Biol. 2021 Jun 4;9:683495. doi: 10.3389/fcell.2021.683495. eCollection 2021.
Collagens are major constituents of the extracellular matrix (ECM) that play an essential role in the structure of the inner ear and provide elasticity and rigidity when the signals of sound are received and transformed into electrical signals. LOXL3 is a member of the lysyl oxidase (LOX) family that are copper-dependent amine oxidases, generating covalent cross-links to stabilize polymeric elastin and collagen fibers in the ECM. Biallelic missense variant of LOXL3 was found in Stickler syndrome with mild conductive hearing loss. However, available information regarding the specific roles of LOXL3 in auditory function is limited. In this study, we showed that the Col2a1-Cre-mediated ablation of Loxl3 in the inner ear can cause progressive hearing loss, degeneration of hair cells and secondary degeneration of spiral ganglion neurons. The abnormal distribution of type II collagen in the spiral ligament and increased inflammatory responses were also found in mice. Amino oxidase activity exerts an effect on collagen; thus, Loxl3 deficiency was expected to result in the instability of collagen in the spiral ligament and the basilar membrane, which may interfere with the mechanical properties of the organ of Corti and induce the inflammatory responses that are responsible for the hearing loss. Overall, our findings suggest that Loxl3 may play an essential role in maintaining hearing function.
胶原蛋白是细胞外基质（ECM）的主要成分，在内耳结构中发挥着重要作用，并在声音信号被接收并转化为电信号时提供弹性和刚性。赖氨酰氧化酶（LOX）家族是一类铜依赖性胺氧化酶，LOXL3是该家族的成员之一，可生成共价交联以稳定ECM中的聚合弹性蛋白和胶原纤维。在患有轻度传导性听力损失的斯蒂克勒综合征患者中发现了LOXL3的双等位基因错义变异。然而，关于LOXL3在听觉功能中的具体作用的现有信息有限。在本研究中，我们表明内耳中Col2a1-Cre介导的Loxl3基因敲除可导致进行性听力损失、毛细胞退化和螺旋神经节神经元的继发性退化。在小鼠中还发现了螺旋韧带中II型胶原蛋白的异常分布以及炎症反应增加。胺氧化酶活性对胶原蛋白有影响；因此，预计Loxl3缺乏会导致螺旋韧带和基底膜中胶原蛋白的不稳定，这可能会干扰柯蒂氏器的机械性能并引发导致听力损失的炎症反应。总体而言，我们的研究结果表明Loxl3可能在维持听力功能中起重要作用。
