Activated hypoxia-inducible factor-1α pathway modulates early events in stretch-induced skin neovascularization via stromal cell-derived factor-1 and vascular endothelial growth factor.

BACKGROUND: Tissue expansion promotes skin regeneration. These responses occur only early after mechanical load and are then replaced by apoptosis-related events during stress relaxation. The mechanism modulating this transient process remains unknown. OBJECTIVE: To elucidate key phenomena that drive early regenerative events after tissue expansion. METHODS: Intraoperative tissue expansion was performed on 25 patients undergoing facial reconstruction. Paired skin biopsies were obtained from an expanded and unexpanded site from each patient. Differentially expressed genes were inspected by microarray and bioinformatic analysis, and dissected by quantitative polymerase chain reaction, Western blot and immunostaining. Paired biopsies from another nine patients undergoing cyclical expansion for 3 months were also investigated. RESULTS: A total of 124 upregulated and 282 downregulated genes were identified. Among them, the biological terms of extracellular matrix organization and blood vessel growth were most significantly enriched, as shown by Gene Ontology analysis. GeneMANIA dissection demonstrated an interactive network highlighted by the canonical hypoxia-inducible factor-1α (HIF-1α) pathway with stromal cell-derived factor-1 (SDF-1) and vascular endothelial growth factor (VEGFA) being the hub genes. Levels of the HIF-1α protein and its targets SDF-1 and VEGFA were elevated in expanded skin, and CD31 and Ki67 expression increased, indicating augmented vascularity and cell proliferation. Trafficking of CD34(+) CD133(+) endothelial progenitor cells was enhanced in skin undergoing long-time cyclical expansion, a phenomenon that was usually modulated by the HIF-1α pathway. CONCLUSIONS: The HIF-1α pathway is quickly activated and modulates early events in stretch-induced skin neovascularization. The effect may be augmented through enhanced endothelial progenitor cells recruitment into the expanded skin.

Suppressive effects of Neiting acupuncture on toothache: an experimental analysis on Fos expression evoked by tooth pulp stimulation in the trigeminal subnucleus pars caudalis and the periaqueductal gray of rats.

To clarify the antinociceptive mechanism of acupuncture on acute pain, c-fos protein (Fos) expression induced by tooth pulp stimulation was immunohistochemically examined in the spinal trigeminal subnucleus pars caudalis (spVc) and the periaqueductal gray (PAG) of rats with or without Neiting acupuncture. The central projection of trigeminal ganglion neurons innervating in the tooth pulp was examined by tract-tracing method with horseradish peroxidase-conjugated wheat germ agglutinin (WGA-HRP). Central terminals from the first maxillary molar tooth were labeled transganglionically in the dorsomedial part of spVc with WGA-HRP. Numerous numbers of Fos-immunoreactive (Fos-ir) cells were found in the spVc and PAG by stimulation of the tooth pulp with acetic acid or saline. Neiting acupuncture significantly reduced the Fos expression in the spVc induced by tooth pulp stimulation. On the other hand, Neiting acupuncture evoked many Fos-ir cells in the PAG. The present results suggest that Neiting acupuncture activated PAG neurons that sent descending inhibitory fibers to medullo-spinal nociceptive neurons, and reduced the number of Fos-expressed neurons in the trigeminal subnucleus pars caudalis mediating noxious information from teeth to the higher central nervous system.

Abnormal renal function in isolated systolic hypertension correlation with ambulatory blood pressure.

Does ambulatory blood pressure correlate with the renal function damage better than clinic blood pressure in isolated systolic hypertension, as has been reported in other target organ involvement in combined systolic/diastolic hypertension? We investigated the correlation of serum beta-2 microglobulin concentration and both 24-h urine beta-2 microglobulin concentration and excretion as measures (suggestive) of glomerular filtration rate and tubular reabsorption, respectively with both ambulatory and clinic blood pressure in 19 health normotensive (68 +/- 4.9 years) and 50 isolated systolic hypertensive elderly individuals (69 +/- 5.4 years). Serum beta-2 microglobulin concentration and 24-h urine beta-2 microglobulin concentration and excretion were higher in the isolated systolic hypertension than in the normotensive group (P < 0.05). In isolated systolic hypertensive patients, 24-h urine beta-2 microglobulin concentration and excretion were related to ambulatory blood pressure (r = 0.32-0.40, P < 0.05), but not to clinic blood pressure; waking systolic blood pressure had the strongest correlation with both 24-h urine beta-2 microglobulin concentration and excretion among derivatives of ambulatory blood pressure (r = 0.35 and 0.40, P < 0.05). We conclude that ambulatory blood pressure, especially waking systolic blood pressure, is superior to clinical blood pressure in predicting renal function impairment, in isolated systolic hypertensive patients.

Relation between weight and body fat's distribution and ambulatory blood pressure in Chinese elderly.

Ninety-five subjects aged 60 years and over underwent casual and ambulatory blood pressure (BP) measurements as well as weight, height, both waist and hip circumferences and both upper arm and thigh circumferences. Most anthropometric variables were significantly correlated with measures of BP. One stepwise regression analysis was applied to reveal that among measures of BP, 24-hour systolic BP had the strongest correlation with waist/hip ratio and awaking diastolic BP the strongest correlation with weight, both waist and hip circumferences and body mass index. Another was used to show that waist/hip ratio was the best overall predictor of systolic BP and weight the best overall predictor of diastolic BP. We suggest that (1) ambulatory BP be superior to casual BP in evaluating effect of weight and body fat's distribution on BP and (2) waist/hip ratio more important than weight in the hypertensive target organ damage and the prognosis of hypertension in Chinese elderly population.