Acoustic Trauma Causes Cochlear Pericyte-to-Myofibroblast–Like Cell Transformation and Vascular Degeneration, and Transplantation of New Pericytes Prevents Vascular Atrophy

Zhiqiang Hou, Lingling Neng, Jinhui Zhang, Jing Cai, Xiaohan Wang, Yunpei Zhang, Ivan A. Lopez, Xiaorui Shi

Research output: Contribution to journalArticle

Abstract

Acoustic trauma disrupts cochlear blood flow and damages sensory hair cells. Damage and regression of capillaries after acoustic trauma have long been observed, but the underlying mechanism of pathology has not been understood. We show herein that loud sound causes change of phenotype from neural/glial antigen 2 positive/α-smooth muscle actin negative to neural/glial antigen 2 positive/α-smooth muscle actin positive in some pericytes (PCs) on strial capillaries that is strongly associated with up-regulation of transforming growth factor-β1. The acoustic trauma also reduced capillary density and increased deposition of matrix proteins, particularly in the vicinity of transformed PCs. In a newly established in vitro three-dimensional endothelial cell (EC) and PC co-culture model, transformed PCs induced thicker capillary–like branches in ECs and increased collagen IV and laminin expression. Transplantation of exogenous PCs derived from neonatal day 10 mouse cochleae to acoustic traumatized cochleae, however, significantly attenuated the decreased vascular density in the stria. Transplantation of PCs pretransfected with adeno-associated virus 1–vascular endothelial growth factor-A165 under control of a hypoxia-response element markedly promotes vascular volume and blood flow, increased proliferation of PCs and ECs, and attenuated loud sound–caused loss in endocochlear potential and hearing. Our results indicate that loud sound–triggered PC transformation contributes to capillary wall thickening and regression, and young PC transplantation effectively rehabilitates the vascular regression and improves hearing.

Original languageEnglish (US)
Pages (from-to)1943-1959
Number of pages17
JournalAmerican Journal of Pathology
Volume190
Issue number9
DOIs
StatePublished - Sep 2020

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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