Immunocytochemical traits of type IV fibrocytes and their possible relations to cochlear function and pathology

J Assoc Res Otolaryngol. 2009 Sep;10(3):369-82. doi: 10.1007/s10162-009-0165-z. Epub 2009 Mar 10.

Abstract

One of the more consistent and least understood changes in the aging human cochlea is the progressive loss of fibrocytes within the spiral ligament. This report presents an animal model for type IV fibrocyte loss, along with immunocytochemical evidence that noise-induced loss of these cells may account for previously unexplained hearing losses. The remarkably low threshold for noise-induced loss of type IV fibrocytes, approximately 24 dB less than the threshold for adjacent hair cell destruction, may account for the prevalence of missing fibrocytes in humans. In mice, changes in the spectrum of traumatizing noise had little effect upon the site of loss of the fibrocytes, suggesting that the primary site of damage that induced the loss was the basal-most cochlear turn, a site expected to be damaged by all three noise bands. Type IV fibrocytes were found to immunostain for connective tissue growth factor (CTGF) and for transforming growth factor beta receptor 3, a receptor that is known to activate CTGF expression. Type IV fibrocytes lack immunostaining for adenosine triphosphatase and connexins that are key players in potassium ion uptake and transmission, which suggests that they play little, if any, role in potassium recycling from perilymphatic space to the endolymphatic space. Consequently, their loss probably does not directly reduce this process. Immunostaining for a receptor for CTGF, low-density-lipoprotein-related protein 1, indicated that CTGF acts as an autocrine and a paracrine agent within the cochlea. The lack of CTGF paracrine effects following noise-induced loss of type IV fibrocytes may account for previously unexplained hearing losses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Animals
  • Cell Death / physiology
  • Cochlea / metabolism*
  • Cochlea / pathology*
  • Connective Tissue Cells / metabolism*
  • Connective Tissue Cells / pathology*
  • Connective Tissue Growth Factor / metabolism
  • Connexins / metabolism
  • Disease Progression
  • Hearing Loss, Noise-Induced / metabolism*
  • Hearing Loss, Noise-Induced / pathology*
  • Male
  • Mice
  • Mice, Inbred CBA
  • Noise / adverse effects
  • Proteoglycans / metabolism
  • Receptors, Transforming Growth Factor beta / metabolism
  • Sodium-Potassium-Chloride Symporters / metabolism
  • Solute Carrier Family 12, Member 2

Substances

  • CCN2 protein, mouse
  • Connexins
  • Proteoglycans
  • Receptors, Transforming Growth Factor beta
  • SLC12A2 protein, human
  • Slc12a2 protein, mouse
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 2
  • Connective Tissue Growth Factor
  • betaglycan
  • Adenosine Triphosphatases