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CD147 required for corneal endothelial lactate transport
Shimin Li1, Tracy T Nguyen1, Joseph A Bonanno1
1School of Optometry, Indiana University, Bloomington, Indiana, United States.
Investigative Ophthalmology & Visual Science
|June 28, 2014
Summary
Silencing CD147 in corneal endothelium reduces monocarboxylate transporters (MCT1/4), impairing lactate efflux. This leads to lactate buildup and corneal edema, highlighting CD147
Area of Science:
- Ophthalmology
- Cell Biology
- Biochemistry
Background:
- CD147 (basigin) acts as a chaperone for monocarboxylate transporters (MCTs), specifically MCT1 and MCT4.
- MCTs are crucial for transporting lactate and protons across cell membranes.
- The role of CD147-MCT interactions in corneal physiology, particularly lactate transport, requires further elucidation.
Purpose of the Study:
- To investigate the role of CD147 in regulating MCT1 and MCT4 expression in the corneal endothelium.
- To determine if CD147-mediated lactate efflux contributes to maintaining corneal clarity.
- To test the hypothesis that silencing CD147 leads to corneal edema.
Main Methods:
- CD147 expression was silenced in rabbit corneas ex vivo using small interfering RNA (siRNA) and in vivo using lentiviral short hairpin RNA (shRNA).
- Expression levels of CD147 and MCTs (MCT1, MCT2, MCT4) were analyzed using Western blot, RT-PCR, and immunofluorescence.
- Functional assessments included measuring lactate-induced cell acidification, corneal lactate efflux, intracellular lactate concentration, and central cornea thickness (CCT).
Main Results:
- CD147 siRNA significantly reduced CD147, MCT1, and MCT4 expression in ex vivo corneas.
- Lactate efflux from corneas was decreased, while intracellular lactate concentration and corneal edema (increased CCT) were elevated after CD147 silencing.
- In vivo CD147 silencing led to increased central cornea thickness and elevated corneal lactate levels, particularly when challenged with a carbonic anhydrase inhibitor.
Conclusions:
- CD147 is essential for the expression and function of MCT1 and MCT4 in corneal endothelial cells.
- Impaired lactate efflux due to CD147 silencing results in lactate accumulation and corneal edema.
- These findings underscore the critical role of CD147-mediated lactate transport in maintaining corneal endothelial function and transparency.
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