Substance P and Thiorphan Synergically Enhance Angiogenesis in Wound Healing

Impaired angiogenesis is a common pathological characteristic of chronic wounds. Therefore, the regulation of angiogenesis is important for proper tissue repair. It was reported that substance P (SP) accelerates wound healing in a skin injury model. SP is degraded by neutral endopeptidase (NEP). Our study shows that systemic co-treatment of SP and thiorphan, an inhibitor of NEP synergically increased the number of α-smooth muscle actin positive-blood vessels in skin wounds. However, there was no synergic improvement in wound contraction and extracellular matrix deposition. Therefore, inhibition of endogenous NEP activity by thiorphan treatment might modulate the effects of SP treatment specifically on accelerating angiogenesis during wound healing. However, the molecular mechanism(s) of the synergic increase in angiogenesis by SP and thiorphan treatment is still unknown.

Expression of CNP/NPR-B axis and NPR-C/NEP elimination pathways in rats with unilateral ureteral obstruction / 临床儿科杂志

Objectives To study the expression features of C-type natriuretic peptide (CNP)/natriuretic peptide receptor-B (NPR-B) axis and two parallel elimination pathways, natriuretic peptide receptor-C (NPR-C) and neutral endopeptidase (NEP) in unilateral ureteral obstruction (UUO) rats. Methods CNP, NPR-B, NPR-C, NEP, Col-IV and type IV collagen (Col-IV) mRNA and proteins were determined by in situ hybridization, real-time PCR, immunohistochemistry and western blot in UUO rats at 24h, 72h, 1w, 2w, 3w, 1m, 2m and 3m. Results CNP expression tended to be higher immediately after ligation and de-clined along with the progression of disease, occurring predominantly in tubular epithelial cells. A high-level CNP may attribute to the elevated expression of NPR-B in the early phase of UUO. Conclusions NEP and NPR participate in the regulation of CNP expression in tubulointerstitial fibrosis. The gradual increased expression of NPR-C and NEP may cause the subsequent de-cline of CNP.

C-type natriuretic peptide:an important effector molecule for renal homeostasis / 中国药理学通报

C-type natriuretic peptide(CNP),mainly expressed in central nervous system and vascular endothelial cells maintains renal homeostasis by autocrine or paracrine pathway,which regulates water-electrolyte metabolism,vascular resistance,glomerular permeability,and cell proliferation.Thus,clarifying the characteristics of CNP metabolism in kidney would appear promising to develop some new prospects for the evaluation of kidney injury and the targeted therapy.

Increased vascular permeability and reduced neutral endopeptidase activity in rat nasal mucosa after ozone exposure / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Exposure to ozone has several effects on the respiratory tract, including airway inflammation and hyperresponsiveness. It has been suggested that these were associated with decreased NEP (neutral endopeptidase) activity. The purpose of this study is to investigate whether ozone exposure increases the vascular permeability in nasal mucosa, and if the vascular permeability is increased, whether it is associated with decreased NEP activity. MATERIALS AND METHODS: Twenty Wistar rats were divided into four experimental groups: control group (group 1), phosphoramidon pretreated group (group 2), ozone exposure (3 ppm for 30 minutes) group (group 3), and phosphoramidon + ozone exposure group (group 4). Sixty minutes after ozone exposure or 10 minutes after phosphoramidon pretreatment, capsaicin (100microgram/kg) was injected via femoral vein. Immediately, nasal lavage fluid was obtained and Evans blue dye was infused via femoral vein. Five minutes later, rats were sacrificed and nasal mucosa was taken. We measured the amount of extravasated Evans blue dye in nasal mucosa, and the concentration of albumin in nasal lavage fluid. RESULTS: Evans blue extravasation were significantly increased in groups 2, 3, and 4 when compared with group 1 (p<0.05), and in group 4 when compared with group 3 (p<0.05). Albumin concentration in nasal lavage fluid was increased in groups 2, 3, and 4, compared with group 1. But, there were no statistically significant differences. CONCLUSION: These results suggest that ozone increases the vascular permeability of nasal mucosa, and this is partially associated with decreased NEP activity after ozone exposure.