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MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar.

Kwan P, Ding J, Tredget EE - PLoS ONE (2015)

Bottom Line: Lower decorin levels were found in hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis.By blocking miR-181b with an antagomiR, it was possible to increase decorin protein expression in dermal fibroblasts.This suggests miR-181b is involved in the differential expression of decorin in skin and wound healing.

View Article: PubMed Central - PubMed

Affiliation: Division of Plastic Surgery, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Wound Healing Research Group, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

ABSTRACT
Hypertrophic scarring is a frequent fibroproliferative complication following deep dermal burns leading to impaired function and lifelong disfigurement. Decorin reduces fibrosis and induces regeneration in many tissues, and is significantly downregulated in hypertrophic scar and normal deep dermal fibroblasts. It was hypothesized that microRNAs in these fibroblasts downregulate decorin and blocking them would increase decorin and may prevent hypertrophic scarring. Lower decorin levels were found in hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis. A decorin 3' un-translated region reporter assay demonstrated microRNA decreased decorin in deep dermal fibroblasts, and microRNA screening predicted miR- 24, 181b, 421, 526b, or 543 as candidates. After finding increased levels of mir-181b in deep dermal fibroblasts, it was demonstrated that TGF-β1 stimulation decreased miR-24 but increased miR-181b and that hypertrophic scar and deep dermis contained increased levels of miR-181b. By blocking miR-181b with an antagomiR, it was possible to increase decorin protein expression in dermal fibroblasts. This suggests miR-181b is involved in the differential expression of decorin in skin and wound healing. Furthermore, blocking miR-181b reversed TGF-β1 induced decorin downregulation and myofibroblast differentiation in hypertrophic scar fibroblasts, suggesting a potential therapy for hypertrophic scar.

No MeSH data available.


Related in: MedlinePlus

Relative expression of miR-181b in matched superficial and deep dermis and site-matched NS and HSc biopsies.Total RNA was extracted from tissue specimens using a chilled pestle and mortar and Trizol for relative quantitation using RT-qPCR. (a) Relative expression of miR-181b in matched superficial and deep dermis of NS (mean ± SEM, n = 3 samples per patient, * P < 0.001). (b) Relative expression of miR-181b in matched NS and HSc (mean ± SEM, n = 3 samples per patient, * P < 0.05, ** P < 0.01).
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pone.0123054.g004: Relative expression of miR-181b in matched superficial and deep dermis and site-matched NS and HSc biopsies.Total RNA was extracted from tissue specimens using a chilled pestle and mortar and Trizol for relative quantitation using RT-qPCR. (a) Relative expression of miR-181b in matched superficial and deep dermis of NS (mean ± SEM, n = 3 samples per patient, * P < 0.001). (b) Relative expression of miR-181b in matched NS and HSc (mean ± SEM, n = 3 samples per patient, * P < 0.05, ** P < 0.01).

Mentions: After identifying miR-181b as a potential downregulator of DCN in vitro, its expression in vivo in tissues known to express less DCN was examined using RT-qPCR of miRNA isolated from site-matched HSc and NS biopsies, and matched deep and superficial dermis. miR-181b was significantly increased in deep as compared to superficial dermis (Fig 4A), and HSc as compared to NS (Fig 4B).


MicroRNA 181b regulates decorin production by dermal fibroblasts and may be a potential therapy for hypertrophic scar.

Kwan P, Ding J, Tredget EE - PLoS ONE (2015)

Relative expression of miR-181b in matched superficial and deep dermis and site-matched NS and HSc biopsies.Total RNA was extracted from tissue specimens using a chilled pestle and mortar and Trizol for relative quantitation using RT-qPCR. (a) Relative expression of miR-181b in matched superficial and deep dermis of NS (mean ± SEM, n = 3 samples per patient, * P < 0.001). (b) Relative expression of miR-181b in matched NS and HSc (mean ± SEM, n = 3 samples per patient, * P < 0.05, ** P < 0.01).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4383602&req=5

pone.0123054.g004: Relative expression of miR-181b in matched superficial and deep dermis and site-matched NS and HSc biopsies.Total RNA was extracted from tissue specimens using a chilled pestle and mortar and Trizol for relative quantitation using RT-qPCR. (a) Relative expression of miR-181b in matched superficial and deep dermis of NS (mean ± SEM, n = 3 samples per patient, * P < 0.001). (b) Relative expression of miR-181b in matched NS and HSc (mean ± SEM, n = 3 samples per patient, * P < 0.05, ** P < 0.01).
Mentions: After identifying miR-181b as a potential downregulator of DCN in vitro, its expression in vivo in tissues known to express less DCN was examined using RT-qPCR of miRNA isolated from site-matched HSc and NS biopsies, and matched deep and superficial dermis. miR-181b was significantly increased in deep as compared to superficial dermis (Fig 4A), and HSc as compared to NS (Fig 4B).

Bottom Line: Lower decorin levels were found in hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis.By blocking miR-181b with an antagomiR, it was possible to increase decorin protein expression in dermal fibroblasts.This suggests miR-181b is involved in the differential expression of decorin in skin and wound healing.

View Article: PubMed Central - PubMed

Affiliation: Division of Plastic Surgery, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Wound Healing Research Group, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

ABSTRACT
Hypertrophic scarring is a frequent fibroproliferative complication following deep dermal burns leading to impaired function and lifelong disfigurement. Decorin reduces fibrosis and induces regeneration in many tissues, and is significantly downregulated in hypertrophic scar and normal deep dermal fibroblasts. It was hypothesized that microRNAs in these fibroblasts downregulate decorin and blocking them would increase decorin and may prevent hypertrophic scarring. Lower decorin levels were found in hypertrophic scar as compared to normal skin, and in deep as compared to superficial dermis. A decorin 3' un-translated region reporter assay demonstrated microRNA decreased decorin in deep dermal fibroblasts, and microRNA screening predicted miR- 24, 181b, 421, 526b, or 543 as candidates. After finding increased levels of mir-181b in deep dermal fibroblasts, it was demonstrated that TGF-β1 stimulation decreased miR-24 but increased miR-181b and that hypertrophic scar and deep dermis contained increased levels of miR-181b. By blocking miR-181b with an antagomiR, it was possible to increase decorin protein expression in dermal fibroblasts. This suggests miR-181b is involved in the differential expression of decorin in skin and wound healing. Furthermore, blocking miR-181b reversed TGF-β1 induced decorin downregulation and myofibroblast differentiation in hypertrophic scar fibroblasts, suggesting a potential therapy for hypertrophic scar.

No MeSH data available.


Related in: MedlinePlus