Substance P enhances wound closure in nitric oxide synthase knockout mice.

Introduction: The neuropeptide, substance P (SP), up-regulates nitric oxide production (NO). The purpose of this study was to determine whether SP enhances response to cutaneous injury in nitric oxide synthase knockout (NOS null) mice.

Methods: We studied mice with targeted deletions of the 3 NOS genes, neuronal NOS, inducible NOS, or endothelial NOS.

Topical substance P increases inflammatory cell density in genetically diabetic murine wounds.

The neuropeptide substance P (SP) is a known inflammatory mediator released from cutaneous peripheral nerve terminals. SP effects on cellular composition in the cutaneous response to injury remain unclear. Based on our previous observations about SP effects on wound repair, we hypothesized that topical SP increases inflammatory cell density infiltration early after injury.

Substance P levels and neutral endopeptidase activity in acute burn wounds and hypertrophic scar.

Background: Substance P, a cutaneous neuroinflammatory mediator released from peripheral nerves, plays a role in responses to injury. Neutral endopeptidase is a cell membrane-bound metallopeptidase enzyme that regulates substance P activity. The question of substance P involvement in hypertrophic scar development has been based on observations that hypertrophic scars have increased numbers of nerves.

Antioxidants inhibit fatty acid and glucose-mediated induction of neutral endopeptidase gene expression in human microvascular endothelial cells.

Background: Neutral endopeptidase (NEP) is a membrane-bound metallopeptidase that degrades tachykinins and may regulate their role in wound repair. NEP enzyme activity is increased in diabetic wounds and skin compared with normal controls. We have shown that unsaturated fatty acids and glucose upregulate NEP activity in human microvascular endothelial cells (HMECs) and that vitamins E and C reduce this effect.

Further similarities between cutaneous scarring in the female, red Duroc pig and human hypertrophic scarring.

Knowledge of the pathophysiology of hypertrophic scarring following deep dermal injuries is minimal due to the lack of an animal model. We previously confirmed that thick scars in female, red Duroc pigs (FRDP) are similar to human hypertrophic scar. The purpose of this study was to evaluate TGFbeta1, IGF-1, decorin, and versican expression in FRDP wounds.

Fatty acids and glucose increase neutral endopeptidase activity in human microvascular endothelial cells.

Neutral endopeptidase (NEP), a membrane-bound metallopeptidase enzyme that degrades neuropeptides, bradykinin, atrial natriuretic factor, enkephalins, and endothelin may regulate response to injury. We have previously demonstrated increased NEP localization and enzyme activity in diabetic wounds and skin compared with normal controls. We hypothesized that hyperlipidemia and hyperglycemia associated with type 2 diabetes mellitus may induce excessive NEP activity and thereby diminish normal response to injury.