Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis.
Cisplatin-Induced Stria Vascularis Damage Is Associated with Inflammation and Fibrosis.
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顺铂引起的血管纹损伤与炎症和纤维化有关
DOI：
10.1155/2020/8851525
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发表时间：
2020
影响因子：
3.1
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Zhang N;Cai J;Xu L;Wang H;Liu W
血管纹（SV）在内耳产生耳蜗内电位（EP），是正常毛细胞（HC）机械传导和听力所必需的。在内耳中，细胞连接对于组成不同的液体室的建立是必不可少的。耳毒性药物顺铂可损伤SV，引起感音神经性听力损失；然而，这种损伤背后的潜在机制尚不清楚。本研究通过小鼠腹腔注射顺铂（3 mg/kg/天，连续7天），通过EP记录和听觉脑干反应（ABR）分析测定听功能，透射电镜（TEM）观察SV超微结构，western blot、PCR和免疫荧光染色检测细胞连接蛋白的表达和分布。我们发现顺铂治疗小鼠EP显著降低，ABR阈值显著升高；顺铂诱导边缘细胞（MCs）、内皮细胞（ECs）、周细胞等超微结构改变。我们发现，顺铂不仅通过降低SV MCs中带状闭塞蛋白-1 （ZO-1）的表达，还通过降低MCs和基底细胞（bc）中连接蛋白26 （Cx26）和连接蛋白43 （Cx43）的表达来损害听觉功能。更重要的是，顺铂诱导血管周围巨噬细胞样黑色素细胞（PVM/Ms）和白细胞介素-1β (IL-1β)的激活，以及层粘连蛋白和胶原IV等促纤维化蛋白的表达增加。因此，我们的研究结果首次表明，顺铂诱导SV纤维化、炎症和细胞连接的复杂表达变化。
The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell (HC) mechanotransduction and hearing. Cell junctions are indispensable for the establishment of compositionally distinct fluid compartments in the inner ear. Ototoxic drug cisplatin can damage SV and cause sensorineural hearing loss; however, the underlying mechanisms behind such injury are unclear. In this study, after the intraperitoneal injection of cisplatin (3 mg/kg/day for 7 days) in mice, we determined the auditory function by EP recording and auditory brainstem response (ABR) analysis, observed the ultrastructure of SV by transmission electron microscopy (TEM), and examined the expression and distribution of cell junction proteins by western blot, PCR, and immunofluorescence staining. We discovered that the EP was significantly reduced while ABR thresholds were significantly elevated in cisplatin-treated mice; cisplatin induced ultrastructural changes in marginal cells (MCs), endothelial cells (ECs), pericytes, etc. We found that cisplatin insulted auditory function not only by reducing the expression of zonula occludens protein-1 (ZO-1) in MCs of the SV but also by decreasing the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in MCs and basal cells (BCs). More importantly, cisplatin induced activations of perivascular-resident macrophage-like melanocytes (PVM/Ms) and interleukin-1beta (IL-1β) as well as increased expressions of profibrotic proteins such as laminin and collagen IV in SV. Thus, our results firstly showed that cisplatin induced fibrosis, inflammation, and the complex expression change of cell junctions in SV.
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影响因子：
2.6
作者：
Lee, Ho Yun;Jung, Su Young;Lee, Sun Kyu
通讯作者：
Lee, Sun Kyu
醛固酮刺激的巨噬细胞上调同种异体移植物炎症因子 1 的表达和分泌，促进肾成纤维细胞形成促纤维化表型
影响因子：
5.4
作者：
Li Y;Wang X;Zhang L;Yuan X;Hao J;Ni J;Hao L
通讯作者：
Hao L
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影响因子：
9
作者：
Liu L;Chen Y;Qi J;Zhang Y;He Y;Ni W;Li W;Zhang S;Sun S;Taketo MM;Wang L;Chai R;Li H
通讯作者：
Li H
影响因子：
2.8
作者：
Alam, SA;Ikeda, K;Takasaka, T
通讯作者：
Takasaka, T
影响因子：
2
作者：
Kalman, M.;Mahalek, J.;Sadeghian, S.
通讯作者：
Sadeghian, S.