Purchase this article with an account.
Diana Gutsaeva, Folami Lamoke, Olga Rafikova, Manuela Bartoli; Rhomboid proteins (iRhom 1 and 2) as new regulators of inflammatory processes in the diabetic retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4296.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Tumor necrosis alpha converting enzyme (TACE/ADAM17) is an important regulator of inflammatory and neuroprotective responses because of its shedding ability towards cytokines, cytokine receptors, and adhesion molecules. We have previously shown that TACE/ADAM17 expression and activity were up-regulated in human and rat diabetic retinas. The purpose of the present study was to identify regulatory mechanisms of TACE-ADAM17 in the hyperglycemic-milieu particularly focusing on members of the rhomboid family of proteases, iRhom1 and 2, that have been shown to regulate TACE/ADAM17 maturation and translocation to the plasma membrane in competent cells.
Streptozotocin-induced diabetic rats (STZ-rats) were kept diabetic for 8 and 12 weeks. Normoglycemic age-matched rats were used as control. Western blotting and immunohistochemical analyses were conducted to assess iRhom 1 and 2 and TACE/ADAM17 expression levels as well as immunolocalization in the rat retinas.<br />
Western blotting analysis revealed that hyperglycemia stimulated the expression of TACE/ADAM17 as well as of iRhom 1 and iRhom 2 in STZ-rat retinas as compared to normoglycemic age-matched control rats. In addition TACE/ADAM17 was immunolocalized around blood vessels and in cells of the inner nuclear layer. IRhom 1 immunoreactivity was highly expressed around blood vessels, whereas iRhom2 was mainly localized in cells of the inner nuclear layer.
Our data show a positive induction of iRhom proteins in the diabetic retina and implicate the maturation process of TACE/ADAM17 in the pro-inflammatory events leading to neurovascular injury in the diabetic retina.<br />
This PDF is available to Subscribers Only