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

Overview

Journal J Assoc Res Otolaryngol

Specialty Otorhinolaryngology

Date 2018 Jun 6

PMID 29869048

Citations 9

Authors

Zhiqiang Hou

Xiaohan Wang

Jing Cai

Jinhui Zhang

Ahmed Hassan

Manfred Auer

Xiaorui Shi

Affiliations

Soon will be listed here.

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.

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References

Fredriksson L, Li H, Eriksson U . The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev. 2004; 15(4):197-204. DOI: 10.1016/j.cytogfr.2004.03.007. View

Neng L, Zhang F, Kachelmeier A, Shi X . Endothelial cell, pericyte, and perivascular resident macrophage-type melanocyte interactions regulate cochlear intrastrial fluid-blood barrier permeability. J Assoc Res Otolaryngol. 2012; 14(2):175-85. PMC: 3660918. DOI: 10.1007/s10162-012-0365-9. View

Facchiano A, De Marchis F, Turchetti E, Facchiano F, Guglielmi M, Denaro A . The chemotactic and mitogenic effects of platelet-derived growth factor-BB on rat aorta smooth muscle cells are inhibited by basic fibroblast growth factor. J Cell Sci. 2000; 113 ( Pt 16):2855-63. DOI: 10.1242/jcs.113.16.2855. View

Liu S, Agalliu D, Yu C, Fisher M . The role of pericytes in blood-brain barrier function and stroke. Curr Pharm Des. 2012; 18(25):3653-62. DOI: 10.2174/138161212802002706. View

Dai M, Shi X . Fibro-vascular coupling in the control of cochlear blood flow. PLoS One. 2011; 6(6):e20652. PMC: 3106013. DOI: 10.1371/journal.pone.0020652. View

Gratton M, Schmiedt R, Schulte B . Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis. Hear Res. 1996; 102(1-2):181-90. DOI: 10.1016/s0378-5955(96)90017-9. View

Sims D . The pericyte--a review. Tissue Cell. 1986; 18(2):153-74. DOI: 10.1016/0040-8166(86)90026-1. View

Salt A, Melichar I, Thalmann R . Mechanisms of endocochlear potential generation by stria vascularis. Laryngoscope. 1987; 97(8 Pt 1):984-91. View

Greenhalgh S, Conroy K, Henderson N . Healing scars: targeting pericytes to treat fibrosis. QJM. 2014; 108(1):3-7. PMC: 4278264. DOI: 10.1093/qjmed/hcu067. View

10.

Greenhalgh S, Iredale J, Henderson N . Origins of fibrosis: pericytes take centre stage. F1000Prime Rep. 2013; 5:37. PMC: 3768328. DOI: 10.12703/P5-37. View

11.

Kim J, Hong K, Song W, Bae D, Hwang I, Kim J . Perivascular Progenitor Cells Derived From Human Embryonic Stem Cells Exhibit Functional Characteristics of Pericytes and Improve the Retinal Vasculature in a Rodent Model of Diabetic Retinopathy. Stem Cells Transl Med. 2016; 5(9):1268-76. PMC: 4996442. DOI: 10.5966/sctm.2015-0342. View

12.

Chen Y, Chang F, Wu C, Chou Y, Hsu H, Chiang W . Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis. Kidney Int. 2011; 80(11):1170-81. DOI: 10.1038/ki.2011.208. View

13.

Pfister F, Feng Y, Vom Hagen F, Hoffmann S, Molema G, Hillebrands J . Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes. 2008; 57(9):2495-502. PMC: 2518502. DOI: 10.2337/db08-0325. View

14.

Choudhury N, Chen F, Shi X, Nuttall A, Wang R . Volumetric Imaging of Blood Flow within Cochlea in Gerbil in vivo. IEEE J Sel Top Quantum Electron. 2010; PP(99):1-6. PMC: 2872492. DOI: 10.1109/JSTQE.2009.2032671. View

15.

Wangemann P . Cochlear blood flow regulation. Adv Otorhinolaryngol. 2002; 59:51-7. DOI: 10.1159/000059241. View

16.

Bell R, Winkler E, Sagare A, Singh I, LaRue B, Deane R . Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010; 68(3):409-27. PMC: 3056408. DOI: 10.1016/j.neuron.2010.09.043. View

17.

Pennock S, Haddock L, Mukai S, Kazlauskas A . Vascular endothelial growth factor acts primarily via platelet-derived growth factor receptor α to promote proliferative vitreoretinopathy. Am J Pathol. 2014; 184(11):3052-68. PMC: 4215028. DOI: 10.1016/j.ajpath.2014.07.026. View

18.

Hirose K, Liberman M . Lateral wall histopathology and endocochlear potential in the noise-damaged mouse cochlea. J Assoc Res Otolaryngol. 2003; 4(3):339-52. PMC: 1805786. DOI: 10.1007/s10162-002-3036-4. View

19.

Cohen-Salmon M, Regnault B, Cayet N, Caille D, Demuth K, Hardelin J . Connexin30 deficiency causes instrastrial fluid-blood barrier disruption within the cochlear stria vascularis. Proc Natl Acad Sci U S A. 2007; 104(15):6229-34. PMC: 1851033. DOI: 10.1073/pnas.0605108104. View

20.

Graf K, Xi X, Yang D, Fleck E, Hsueh W, Law R . Mitogen-activated protein kinase activation is involved in platelet-derived growth factor-directed migration by vascular smooth muscle cells. Hypertension. 1997; 29(1 Pt 2):334-9. DOI: 10.1161/01.hyp.29.1.334. View