Have a look at this very interesting manuscript published today from a Birmingham UK team. It is yet another interesting bit of data giving insight into the potential role of retinoids in diabetic (or perhaps just diseased, chronically inflamed) skin.
|a||School of Clinical and Experimental Medicine, University of Birmingham, B15 2TT Birmingham, UK|
|b||Heart of England NHS Foundation Trust, B9 5SS Birmingham, UK|
|c||Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Received 21 April 2011; revised 11 August 2011; Accepted 7 October 2011. Available online 4 November 2011.
In diabetes, foot ulceration may result from increased skin fragility. Retinoids can reverse some diabetes-induced deficits of skin structure and function, but their clinical utility is limited by skin irritation. The effects of diabetes and MDI 301, a nonirritating synthetic retinoid, and retinoic acid have been evaluated on matrix metalloproteinases (MMPs), procollagen expression, and skin structure in skin biopsies from nondiabetic volunteers and diabetic subjects at risk of foot ulceration using organ culture techniques.
Zymography and enzyme-linked immunosorbent assay were utilized for analysis of MMP-1, -2, and -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) and immunohistochemistry for type I procollagen protein abundance. Collagen structure parameters were assessed in formalin-fixed, paraffin-embedded tissue sections.
The % of active MMP-1 and -9 was higher and TIMP-1 abundance was lower in subjects with diabetes. Type 1 procollagen abundance was reduced and skin structural deficits were increased in diabetes. Three μM MDI 301 reduced active MMP-1 and -9 abundance by 29% (P<.05) and 40% (P<.05), respectively, and increased TIMP-1 by 45% (P=.07). MDI 301 increased type 1 procollagen abundance by 40% (P<.01) and completely corrected structural deficit scores. Two μM retinoic acid reduced MMP-1 but did not significantly affect skin structure.
These data indicate that diabetic patients at risk of foot ulceration have deficits of skin structure and function. MDI 301 offers potential for repairing this skin damage complicating diabetes.
Keywords: Diabetes; Skin; Retinoids; Foot ulceration