TY - JOUR
T1 - Perivascular macrophage-like melanocyte responsiveness to acoustic trauma-a salient feature of strial barrier associated hearing loss
AU - Zhang, Fei
AU - Dai, Min
AU - Neng, Lingling
AU - Zhang, Jin Hui
AU - Zhi, Zhongwei
AU - Fridberger, Anders
AU - Shi, Xiaorui
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - Acoustic trauma
KW - Endothelial cell
KW - Instrastrial fluidblood barrier
KW - Mouse cochlea
KW - Paracellular permeability
UR - http://www.scopus.com/inward/record.url?scp=84883354990&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883354990&partnerID=8YFLogxK
U2 - 10.1096/fj.13-232892
DO - 10.1096/fj.13-232892
M3 - Article
C2 - 23729595
AN - SCOPUS:84883354990
SN - 0892-6638
VL - 27
SP - 3730
EP - 3740
JO - FASEB Journal
JF - FASEB Journal
IS - 9
ER -