Perivascular macrophage-like melanocyte responsiveness to acoustic trauma-a salient feature of strial barrier associated hearing loss

Fei Zhang, Min Dai, Lingling Neng, Jin Hui Zhang, Zhongwei Zhi, Anders Fridberger, Xiaorui Shi

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Tissue perivascular resident macrophages (PVM/Ms), a hybrid cell type with characteristics of both macrophages and melanocytes, are critical for establishing and maintaining the endocochlear potential (EP) required for hearing. The PVM/Ms modulate expression of tight- and adherens-junction proteins in the endothelial barrier of the stria vascularis (intrastrial fluid-blood barrier) through secretion of a signaling molecule, pigment epithelium growth factor (PEDF). Here, we identify a significant link between abnormalities in PVM/Ms and endothelial barrier breakdown from acoustic trauma to the mouse ear. We find that acoustic trauma causes activation of PVM/Ms and physical detachment from capillary walls. Concurrent with the detachment, we find loosened tight junctions between endothelial cells and decreased production of tight- and adherens-junction protein, resulting in leakage of serum proteins from the damaged barrier. A key factor in the intrastrial fluid-blood barrier hyperpermeability exhibited in the mice is downregulation of PVM/M modulated PEDF production. We demonstrate that delivery of PEDF to the damaged ear ameliorates hearing loss by restoring intrastrial fluidblood barrier integrity. PEDF up-regulates expression of tight junction-associated proteins (ZO-1 and VE-cadherin) and PVM/M stabilizing neural cell adhesion molecule (NCAM-120). These studies point to the critical role PVM/Ms play in regulating intrastrial fluid-blood barrier integrity in healthy and noise-damaged ears.-Zhang, F., Dai, M., Neng, L., Zhang, J.H., Zhi, Z., Fridberger, A., Shi, X. Perivascular macrophage-like melanocyte responsiveness to acoustic trauma- a salient feature of strial barrier associated hearing loss.

Original languageEnglish (US)
Pages (from-to)3730-3740
Number of pages11
JournalFASEB Journal
Volume27
Issue number9
DOIs
StatePublished - Sep 2013

Keywords

  • Acoustic trauma
  • Endothelial cell
  • Instrastrial fluidblood barrier
  • Mouse cochlea
  • Paracellular permeability

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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