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Jerome mauris, Julia Dieckow, Eric E Gabison, Romana A Nowak, Pablo Argueso; CD147 is Required for Meibomian Gland Development and Differentiation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5493.
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Meibomian glands produce lipids for the tear film, preventing evaporation and maintaining ocular surface homeostasis. CD147 is a transmembrane protein known to regulate expression of matrix metalloproteinases (MMPs), which are known to be central in meibomian gland morphogenesis. The goal of this study was to determine the role of CD147 in meibomian gland development and differentiation.
The expression and distribution of CD147 in human meibomian glands was evaluated by immunofluorescence microscopy. Telomerase-transformed human meibomian gland (iHMG) epithelial cells were grown in serum-containing medium for 7 days to induce differentiation. CD147 expression was abrogated using siRNA and protein levels were monitored by western blot analysis. Cell proliferation was assessed by flow cytometry and immunostaining using BrdU and a Ki-67 antibody, respectively. Histology was performed on eyelid sections corresponding to the central corneal region of CD147 knockout and wild-type mice using toluidine blue. Cell differentiation was evaluated via neutral lipid production using LipidTOX™ and Oil Red-O staining.
CD147 localized primarily to basal cells at the peripheral margin of secretory acini in the human meibomian gland. Abrogation of CD147 expression by siRNA in iHMG cells decreased CD147 protein levels by 80%, concomitant with reduction of proliferation and the ability to produce neutral lipids. Meibomian glands of CD147 knockout mice had a lower number of acini in both the superior and inferior tarsal plates of the eyelids, which appeared to be smaller in size than those of wild-type mice. Moreover, Ki-67 and Oil Red-O staining were reduced in the glands of knockout mice, indicating impaired proliferation and meibocyte differentiation.
The metalloproteinase inducer CD147 influences meibomian gland development and differentiation. Alteration of CD147 expression might be involved in the ocular surface pathology leading to meibomian gland dysfunction.
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