The presence of B-type natriuretic peptide in burns and the responsiveness of fibroblasts to BNP: proof of principle

B-type natriuretic peptide (BNP) released from cardiac myocytes plays an important role in cardiac homeostasis through cyclic guanosine monophosphate (cGMP) activation. BNP also reduces cardiac remodeling and fibrosis. The antifibrotic effects of BNP are mediated in part by blocking the effects of t...

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Bibliographic Details
Published in:Academic emergency medicine 2007-06, Vol.14 (6), p.503-507
Main Authors: Singer, Adam J, Jurukovski, Vladimir, Simon, Marcia, Ma, Jing Ying, Protter, Andrew, Arura, Balvantray, Soroff, Harry S
Format: Article
Language:English
Subjects:
Analysis of Variance
Burns
Burns - metabolism
Cell growth
Cells, Cultured
Clinical outcomes
Fibroblasts - drug effects
Fibroblasts - metabolism
Humans
Immunoenzyme Techniques
In Vitro Techniques
Keratinocytes - drug effects
Keratinocytes - metabolism
Natriuretic Peptide, Brain - pharmacology
Natriuretic Peptide, Brain - secretion
Peptides
Pilot Projects
Skin
Skin - metabolism
Wound healing
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Summary:B-type natriuretic peptide (BNP) released from cardiac myocytes plays an important role in cardiac homeostasis through cyclic guanosine monophosphate (cGMP) activation. BNP also reduces cardiac remodeling and fibrosis. The antifibrotic effects of BNP are mediated in part by blocking the effects of transforming growth factor beta, a profibrotic cytokine that plays a significant role in cutaneous wound healing. It is unclear if BNP plays any role in cutaneous wound healing. To investigate if BNP levels would be elevated in thermally injured human skin and if human-derived fibroblasts would respond to BNP exposure by increasing levels of cGMP. This was an in vitro analysis of human skin. Skin samples and cells were collected from patients with and without thermal injury. The authors stained three skin samples from normal skin (taken at the time of elective cosmetic surgery) with antibodies to BNP and compared these with three tissue samples obtained from burned human skin taken during tangential excision of deep burns. Normal human-derived fibroblasts and keratinocytes were exposed in triplicate to BNP in vitro, and cGMP accumulation was evaluated. Levels of cGMP were quantified and compared with analysis of variance. BNP was present in all specimens of thermally injured skin (especially around collagen, epithelial cells, and endothelial cells) but not in any uninjured skin samples (p = 0.05, single-tailed Fisher's exact test). In vitro grown fibroblasts showed significant increases of cGMP levels with increasing levels of BNP exposure (mean [+/-SD]: 0.6 [+/-0.3], 1.2 [+/-0.2], 4.6 [+/-0.1], and 5.0 [+/-0.9] pmol/mL with BNP concentrations of 0, 10, 500, and 1,000 nmol/L, respectively; p < 0.001). The effect of BNP on keratinocytes was minimal and below the level of quantification. These findings demonstrate proof of principle that human fibroblasts are responsive to the effects of BNP in vitro and that BNP is present in injured skin, suggesting that BNP may play a role in cutaneous wound healing.
ISSN:1069-6563
1553-2712
DOI:10.1111/j.1553-2712.2007.tb01819.x