Platelet-Derived Growth Factor Subunit B Signaling Promotes Pericyte Migration in Response to Loud Sound in the Cochlear Stria Vascularis

Zhiqiang Hou, Xiaohan Wang, Jing Cai, Jinhui Zhang, Ahmed Hassan, Manfred Auer, Xiao Shi

Research output: Contribution to journalArticle

Abstract

Normal blood supply to the cochlea is critical for hearing. Noise damages auditory sensory cells and has a marked effect on the microvasculature in the cochlear lateral wall. Pericytes in the stria vascularis (strial pericytes) are particularly vulnerable and sensitive to acoustic trauma. Exposure of NG2DsRedBAC transgenic mice (6–8 weeks old) to wide-band noise at a level of 120 dB for 3 h per day for 2 consecutive days produced a significant hearing threshold shift and caused pericytes to protrude and migrate from their normal endothelial attachment sites. The pericyte migration was associated with increased expression of platelet-derived growth factor beta (PDGF-BB). Blockade of PDGF-BB signaling with either imatinib, a potent PDGF-BB receptor (PDGFR) inhibitor, or APB5, a specific PDGFRβ blocker, significantly attenuated the pericyte migration from strial vessel walls. The PDGF-BB-mediated strial pericyte migration was further confirmed in an in vitro cell migration assay, as well as in an in vivo live animal model used in conjunction with confocal fluorescence microscopy. Pericyte migration took one of two different forms, here denoted protrusion and detachment. The protrusion is characterized by pericytes with a prominent triangular shape, or pericytes extending fine strands to neighboring capillaries. The detachment is characterized by pericyte detachment and movement away from vessels. We also found the sites of pericyte migration highly associated with regions of vascular leakage. In particular, under transmission electron microscopy (TEM), multiple vesicles at the sites of endothelial cells with loosely attached pericytes were observed. These data show that cochlear pericytes are markedly affected by acoustic trauma, causing them to display abnormal morphology. The effect of loud sound on pericytes is mediated by upregulation of PDGF-BB. Normal functioning pericytes are required for vascular stability.

Original languageEnglish (US)
Pages (from-to)1-17
Number of pages17
JournalJARO - Journal of the Association for Research in Otolaryngology
DOIs
StateAccepted/In press - Jun 4 2018

Fingerprint

Stria Vascularis
Proto-Oncogene Proteins c-sis
Pericytes
Cochlea
Noise-Induced Hearing Loss
Platelet-Derived Growth Factor Receptors
Hearing
Blood Vessels
Noise
Cell Migration Assays
Platelet-Derived Growth Factor

Keywords

  • loud sound
  • mouse cochlea
  • pericyte
  • stria vascularis

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Sensory Systems

Cite this

Platelet-Derived Growth Factor Subunit B Signaling Promotes Pericyte Migration in Response to Loud Sound in the Cochlear Stria Vascularis. / Hou, Zhiqiang; Wang, Xiaohan; Cai, Jing; Zhang, Jinhui; Hassan, Ahmed; Auer, Manfred; Shi, Xiao.

In: JARO - Journal of the Association for Research in Otolaryngology, 04.06.2018, p. 1-17.

Research output: Contribution to journalArticle

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