Loss of epithelial hypoxia-inducible factor prolyl hydroxylase 2 accelerates skin wound healing in mice.

Skin wound healing in mammals is a complex, multicellular process that depends on the precise supply of oxygen. Hypoxia-inducible factor (HIF) prolyl hydroxylase 2 (PHD2) serves as a crucial oxygen sensor and may therefore play an important role during reepithelialization. Hence, this study was aimed at understanding the role of PHD2 in cutaneous wound healing using different lines of conditionally deficient mice specifically lacking PHD2 in inflammatory, vascular, or epidermal cells. Interestingly, PHD2 deficiency only in keratinocytes and not in myeloid or endothelial cells was found to lead to faster wound closure, which involved enhanced migration of the hyperproliferating epithelium. We demonstrate that this effect relies on the unique expression of ß3-integrin in the keratinocytes around the tip of the migrating tongue in an HIF1α-dependent manner. Furthermore, we show enhanced proliferation of these cells in the stratum basale, which is directly related to their attenuated transforming growth factor ß signaling. Thus, loss of the central oxygen sensor PHD2 in keratinocytes stimulates wound closure by prompting skin epithelial cells to migrate and proliferate. Inhibition of PHD2 could therefore offer novel therapeutic opportunities for the local treatment of cutaneous wounds.

The Clock Reading Test: validation of an instrument for the diagnosis of dementia and disorders of visuo-spatial cognition.

BACKGROUND: The 12-item Clock Reading Test (CRT) allows a fine-graded assessment of clock-reading ability. It has a strong focus on visuo-spatial processing and requires no executive processing. This study evaluated the reliability, validity, sensitivity and specificity of the CRT for the diagnosis of dementia and visuo-spatial dysfunction. METHODS: The CRT, the Clock Drawing Test (CDT) and other tests were applied to groups of 200 subjects with dementia, 105 subjects with mild cognitive impairment (MCI), 20 subjects with focal parietal lesions and 64 elderly control subjects. RESULTS: The CRT was found to be reliable and sensitive for the detection of cognitive impairment in parietal lesions, Alzheimer-, mixed- and Lewy Body dementia. Normal subjects and patients with MCI, frontotemporal dementia or cerebral small vessel disease showed little or no impairment. CONCLUSION: CRT and CDT are clock-processing tests with different demand profiles. They can supplement each other in the neuropsychological diagnosis of dementia and visuo-spatial dysfunction.