Loss of CD147 results in impaired epithelial cell differentiation and malformation of the meibomian gland

Cell Death Dis. 2015 Apr 16;6(4):e1726. doi: 10.1038/cddis.2015.98.

Abstract

Meibomian gland dysfunction is a leading cause of ocular surface disease. However, little is known about the regulatory processes that control the development and maintenance of this sebaceous gland. Here, we identify a novel function for CD147, a transmembrane protein that promotes tissue remodeling through induction of matrix metalloproteinases, in regulating meibocyte differentiation and activity. We found that CD147 localized along basal cells and within discrete membrane domains of differentiated meibocytes in glandular acini containing gelatinolytic activity. Induction of meibocyte differentiation in vitro promoted CD147 clustering and MMP9 secretion, whereas RNAi-mediated abrogation of CD147 impaired MMP9 secretion, concomitant with a reduction in the number of proliferative cells and cytoplasmic lipids. Meibomian glands of CD147 knockout mice had a lower number of acini in both the superior and inferior tarsal plates of the eyelids, and were characterized by loss of lipid-filled meibocytes compared with control mice. Together, our data provide evidence showing that gelatinolytic activity in meibocytes is dependent on CD147, and supports a role for CD147 in maintaining the normal development and function of the meibomian gland.

Publication types

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

MeSH terms

  • Animals
  • Basigin / metabolism*
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Humans
  • Meibomian Glands / cytology*
  • Meibomian Glands / metabolism*
  • Meibomian Glands / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout

Substances

  • Basigin