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Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators.

Sirimahachaiyakul P, Sood RF, Muffley LA, Seaton M, Lin CT, Qiao L, Armaly JS, Hocking AM, Gibran NS - PLoS ONE (2015)

Bottom Line: Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery.Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium.Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring.

View Article: PubMed Central - PubMed

Affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.

ABSTRACT

Introduction: Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses.

Methods and materials: Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs) across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium.

Results: Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium.

Discussion: Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring.

No MeSH data available.


Related in: MedlinePlus

Dermal-fibroblast-derived paracrine signaling inhibits melanocyte proliferation.Melanocyte proliferation varied significantly across melanocyte lineages at baseline (p = 0.0002). Dermal fibroblast-conditioned medium significantly inhibited melanocyte proliferation at 48 hours (p<0.0001), and the degree of inhibition varied significantly between samples (p = 0.05). The data in this graph represents a single experiment in which N = 4; the experiment was reproduced three times. Statistical analysis was based on average values across all six melanocyte lineages rather than individual sample responses to fibroblast-conditioned medium (see Methods).
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pone.0139135.g004: Dermal-fibroblast-derived paracrine signaling inhibits melanocyte proliferation.Melanocyte proliferation varied significantly across melanocyte lineages at baseline (p = 0.0002). Dermal fibroblast-conditioned medium significantly inhibited melanocyte proliferation at 48 hours (p<0.0001), and the degree of inhibition varied significantly between samples (p = 0.05). The data in this graph represents a single experiment in which N = 4; the experiment was reproduced three times. Statistical analysis was based on average values across all six melanocyte lineages rather than individual sample responses to fibroblast-conditioned medium (see Methods).

Mentions: Baseline proliferation varied significantly across melanocyte samples (p = 0.0002; Fig 4). Fibroblast-conditioned medium significantly decreased melanocyte proliferation (p<0.0001); the magnitude of the decrease differed significantly between samples (p = 0.05). Similarly, dendricity decreased in response to fibroblast-conditioned medium across samples (Fig 5a). Average dendrite length (Fig 5b) varied significantly across untreated samples (p<0.0001) and decreased significantly in response to fibroblast-conditioned medium (p = 0.005); the magnitude of the decrease varied based on sample (p = 0.04). The proportion of multipolar cells (>2 dendrites) also varied significantly at baseline (Fig 5c; p = 0.002) and decreased in response to conditioned medium, with the magnitude of the reduction dependent on the melanocyte sample (p<0.0001). These data have clinical implications, since dendrites are critical for transfer of melanosomes to keratinocytes and dendrite number determines melanocyte activity in terms of pigment production [13,31,32]. We have previously published evidence that conditioned medium modulates endothelial cell and fibroblast in vitro responses. [33,34] This coupled with the observation that melanocyte isolate phenotypic responses differed from one another and depending on the read-out suggests that the responses are not artifacts of conditioned medium.


Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators.

Sirimahachaiyakul P, Sood RF, Muffley LA, Seaton M, Lin CT, Qiao L, Armaly JS, Hocking AM, Gibran NS - PLoS ONE (2015)

Dermal-fibroblast-derived paracrine signaling inhibits melanocyte proliferation.Melanocyte proliferation varied significantly across melanocyte lineages at baseline (p = 0.0002). Dermal fibroblast-conditioned medium significantly inhibited melanocyte proliferation at 48 hours (p<0.0001), and the degree of inhibition varied significantly between samples (p = 0.05). The data in this graph represents a single experiment in which N = 4; the experiment was reproduced three times. Statistical analysis was based on average values across all six melanocyte lineages rather than individual sample responses to fibroblast-conditioned medium (see Methods).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4587942&req=5

pone.0139135.g004: Dermal-fibroblast-derived paracrine signaling inhibits melanocyte proliferation.Melanocyte proliferation varied significantly across melanocyte lineages at baseline (p = 0.0002). Dermal fibroblast-conditioned medium significantly inhibited melanocyte proliferation at 48 hours (p<0.0001), and the degree of inhibition varied significantly between samples (p = 0.05). The data in this graph represents a single experiment in which N = 4; the experiment was reproduced three times. Statistical analysis was based on average values across all six melanocyte lineages rather than individual sample responses to fibroblast-conditioned medium (see Methods).
Mentions: Baseline proliferation varied significantly across melanocyte samples (p = 0.0002; Fig 4). Fibroblast-conditioned medium significantly decreased melanocyte proliferation (p<0.0001); the magnitude of the decrease differed significantly between samples (p = 0.05). Similarly, dendricity decreased in response to fibroblast-conditioned medium across samples (Fig 5a). Average dendrite length (Fig 5b) varied significantly across untreated samples (p<0.0001) and decreased significantly in response to fibroblast-conditioned medium (p = 0.005); the magnitude of the decrease varied based on sample (p = 0.04). The proportion of multipolar cells (>2 dendrites) also varied significantly at baseline (Fig 5c; p = 0.002) and decreased in response to conditioned medium, with the magnitude of the reduction dependent on the melanocyte sample (p<0.0001). These data have clinical implications, since dendrites are critical for transfer of melanosomes to keratinocytes and dendrite number determines melanocyte activity in terms of pigment production [13,31,32]. We have previously published evidence that conditioned medium modulates endothelial cell and fibroblast in vitro responses. [33,34] This coupled with the observation that melanocyte isolate phenotypic responses differed from one another and depending on the read-out suggests that the responses are not artifacts of conditioned medium.

Bottom Line: Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery.Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium.Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring.

View Article: PubMed Central - PubMed

Affiliation: University of Washington Department of Surgery, Seattle, Washington, United States of America.

ABSTRACT

Introduction: Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses.

Methods and materials: Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs) across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium.

Results: Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium.

Discussion: Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring.

No MeSH data available.


Related in: MedlinePlus