Deficit of mitogen-activated protein phosphatase 1 (DUSP1) accelerates progressive hearing loss

被引：19

作者：

Celaya, Adelaide M. ^{[1
,2
]}

Sanchez-Perez, Isabel ^{[1
,2
,3
,4
,5
]}

Bermudez-Munoz, Jose M. ^{[1
,2
]}

Rodriguez-de la Rosa, Lourdes ^{[1
,2
,3
]}

Pintado-Berninches, Laura ^{[1
,3
]}

Perona, Rosario ^{[1
,2
,3
]}

Murillo-Cuesta, Silvia ^{[1
,2
]}

Varela-Nieto, Isabel ^{[1
,2
]}

机构：

[1] Autonomous Univ Madrid CSIC UAM, Inst Biomed Res Alberto Sols IIBM, Spanish Natl Res Council, Madrid, Spain

[2] Ctr Biomed Network Res Rare Dis CIBERER, ISCIII, CIBER, Madrid, Spain

[3] Hosp La Paz, Inst Hlth Res IdiPAZ, Madrid, Spain

[4] Autonomous Univ Madrid, Fac Med, Biochem Dept, Madrid, Spain

[5] UCLM CSIC, Biomed Unit, Madrid, Spain

来源：

ELIFE | 2019年 / 8卷

关键词：

DUAL-SPECIFICITY PHOSPHATASES; KIDNEY INJURY MOLECULE-1; NOISE-INDUCED CHANGES; MAP KINASE; INNER-EAR; HAIR-CELLS; NULL MICE; EXPRESSION; STRESS; MKP-1;

D O I：

10.7554/eLife.39159

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mitogen-activated protein kinases (MAPK) such as p38 and the c-Jun N-terminal kinases (JNKs) are activated during the cellular response to stress signals. Their activity is regulated by the MAPK-phosphatase 1 (DUSP1), a key component of the anti-inflammatory response. Stress kinases are well-described elements of the response to otic injury and the otoprotective potential of JNK inhibitors is being tested in clinical trials. By contrast, there are no studies exploring the role of DUSP1 in hearing and hearing loss. Here we show that Dusp1 expression is age-regulated in the mouse cochlea. Dusp1 gene knock-out caused premature progressive hearing loss, as confirmed by auditory evoked responses in Dusp1(-/-) mice. Hearing loss correlated with cell death in hair cells, degeneration of spiral neurons and increased macrophage infiltration. Dusp1(-/-) mouse cochleae showed imbalanced redox status and dysregulated expression of cytokines. These data suggest that DUSP1 is essential for cochlear homeostasis in the response to stress during ageing.

引用

页数：28

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