Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/24909
Title: Temperature oscillations drive cycles in the activity of MMP-2,9 secreted by a human trabecular meshwork cell line
Authors: Li, SKL
Banerjee, J
Jang, C
Sehga, A
Stone, RA
Civan, MM
Keywords: Circadian rhythm
Matrix metalloproteinases
Trabecular outflow
Issue Date: 2015
Publisher: Association for Research in Vision and Ophthalmology Inc.
Source: Investigative ophthalmology and visual science, 2015, v. 56, no. 2, p. 1396-1405 How to cite?
Journal: Investigative Ophthalmology and Visual Science 
Abstract: PURPOSE. Aqueous humor inflow falls 50% during sleeping hours without proportional fall in IOP, partly reflecting reduced outflow facility. The mechanisms underlying outflow facility cycling are unknown. One outflow facility regulator is matrix metalloproteinase (MMP) release from trabecular meshwork (TM) cells. Because anterior segment temperature must oscillate due to core temperature cycling and eyelid closure during sleep, we tested whether physiologically relevant temperature oscillations drive cycles in the activity of secreted MMP. METHODS. Temperature of transformed normal human TM cells (hTM5 line) was fixed or alternated 12 hours/12 hours between 338C and 378C. Activity of secreted MMP-2 and MMP-9 was measured by zymography, and gene expression by RT-PCR and quantitative PCR. RESULTS. Raising temperature to 378C increased, and lowering to 338C reduced, activity of secreted MMP. Switching between 378C and 338C altered MMP-9 by 40% 6 3% and MMP-2 by 22% 6 2%. Peripheral circadian clocks did not mediate temperature-driven cycling of MMP secretion because MMP-release oscillations did not persist at constant temperature after 3 to 6 days of alternating temperatures, and temperature cycles did not entrain clock-gene expression in these cells. Furthermore, inhibiting heat shock transcription factor 1, which links temperature and peripheral clock-gene oscillations, inhibited MMP-9 but not MMP-2 temperature-driven MMP cycling. Inhibition of heat-sensitive TRPV1 channels altered total MMP secretion but not temperature-induced modulations. Inhibiting cold-sensitive TRPM-8 channels had no effect. CONCLUSIONS. Physiologically relevant temperature oscillations drive fluctuations of secreted MMP-2 and MMP-9 activity in hTM5 cells independent of peripheral clock genes and temperature-sensitive TRP channels.
URI: http://hdl.handle.net/10397/24909
ISSN: 0146-0404
DOI: 10.1167/iovs.14-15834
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