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MicroRNA-23b Inhibits the Proliferation and Migration of Heat-Denatured Fibroblasts by Targeting Smad3.

Zhang X, Yang J, Zhao J, Zhang P, Huang X - PLoS ONE (2015)

Bottom Line: MicroRNAs (miRNA) are small noncoding RNAs and regulate normal physiology as well as disease development.In addition, miR-23b modulated denatured dermis by activating the Notch1 and TGF-β signaling pathways.Our findings suggest that downregulation of miR-23b contributes to the recovery of denatured dermis, which may be valuable for treatment of skin burns.

View Article: PubMed Central - PubMed

Affiliation: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

ABSTRACT

Background: Skin grafting with the preservation of denatured dermis is a novel strategy for the treatment of burn-injured skin. Denatured dermis has the ability to restore to the morphology and function of normal skin, but the underlying molecular mechanism is elusive. MicroRNAs (miRNA) are small noncoding RNAs and regulate normal physiology as well as disease development. In this study, we assessed the potential role of miRNA-23b (miR-23b) in the regulation of cell proliferation and migration of heat-denatured fibroblasts and identified the underlying mechanism.

Methods: The expression of miR-23b in denatured dermis and heat-denatured fibroblasts was detected by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-23b on cell proliferation and migration of heat-denatured fibroblasts were assessed by transient transfection of miR-23b mimics and inhibitor. The target gene of miR-23b and the downstream pathway were further investigated.

Results: miR-23b was downregulated in denatured dermis and heat-denatured fibroblasts. Downregulation of miR-23b dramatically promoted the proliferation and migration of heat-denatured fibroblasts. Subsequent analyses demonstrated that Smad3 was a direct and functional target of miR-23b in heat-denatured fibroblasts, which was validated by the dual luciferase reporter assay. Moreover, immunohistochemistry analysis showed that denatured dermis from rats displayed enhanced staining of Smad3. In addition, miR-23b modulated denatured dermis by activating the Notch1 and TGF-β signaling pathways.

Conclusions: Our findings suggest that downregulation of miR-23b contributes to the recovery of denatured dermis, which may be valuable for treatment of skin burns.

No MeSH data available.


Related in: MedlinePlus

Histological examination of denatured dermis and the expression of miR-23b in denatured dermis.(A) HE staining of denatured dermis 3 days following heat damage revealed nucleus pyknosis of the epidermal and follicular epithelial cells, disintegration of the sebaceous gland, and swelling and fusion of collagen compared to normal skin. (B) The relative expression level of miR-23b was examined by quantitative RT-PCR in normal rat skin (NC), and denatured dermis at different recovery times (1, 3, 5, 7 days) after burn creation. Data are shown as mean ± SD derived from three independent experiments. **, P<0.01, versus NC.
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pone.0131867.g001: Histological examination of denatured dermis and the expression of miR-23b in denatured dermis.(A) HE staining of denatured dermis 3 days following heat damage revealed nucleus pyknosis of the epidermal and follicular epithelial cells, disintegration of the sebaceous gland, and swelling and fusion of collagen compared to normal skin. (B) The relative expression level of miR-23b was examined by quantitative RT-PCR in normal rat skin (NC), and denatured dermis at different recovery times (1, 3, 5, 7 days) after burn creation. Data are shown as mean ± SD derived from three independent experiments. **, P<0.01, versus NC.

Mentions: To explore the expression of miR-23b during the recovery of denatured dermis, the skin tissues of the deep partial-thickness burn rats were collected at different time points after burn creation and stained with hematoxylin and eosin (HE). Three days following burn creation, skin tissues showed pathological characteristics of a deep partial-thickness burn wound including nucleus pyknosis of the epidermal and follicular epithelial cells, disintegration of the sebaceous gland, and swelling and fusion of collagen (Fig 1A). Next, the expression of miR-23b in the denatured dermis was measured at different recovery time points after burn creation (1, 3, 5, and 7 days) by RT-PCR. As shown in Fig 1B, miR-23b expression demonstrated a dynamic alteration during the recovery of denatured dermis. Compared with that of normal skin, miR-23b expression significantly decreased in denatured dermis, with the greatest inhibitory rate of 81% after three days, but then gradually increased three days post-burn.


MicroRNA-23b Inhibits the Proliferation and Migration of Heat-Denatured Fibroblasts by Targeting Smad3.

Zhang X, Yang J, Zhao J, Zhang P, Huang X - PLoS ONE (2015)

Histological examination of denatured dermis and the expression of miR-23b in denatured dermis.(A) HE staining of denatured dermis 3 days following heat damage revealed nucleus pyknosis of the epidermal and follicular epithelial cells, disintegration of the sebaceous gland, and swelling and fusion of collagen compared to normal skin. (B) The relative expression level of miR-23b was examined by quantitative RT-PCR in normal rat skin (NC), and denatured dermis at different recovery times (1, 3, 5, 7 days) after burn creation. Data are shown as mean ± SD derived from three independent experiments. **, P<0.01, versus NC.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4496062&req=5

pone.0131867.g001: Histological examination of denatured dermis and the expression of miR-23b in denatured dermis.(A) HE staining of denatured dermis 3 days following heat damage revealed nucleus pyknosis of the epidermal and follicular epithelial cells, disintegration of the sebaceous gland, and swelling and fusion of collagen compared to normal skin. (B) The relative expression level of miR-23b was examined by quantitative RT-PCR in normal rat skin (NC), and denatured dermis at different recovery times (1, 3, 5, 7 days) after burn creation. Data are shown as mean ± SD derived from three independent experiments. **, P<0.01, versus NC.
Mentions: To explore the expression of miR-23b during the recovery of denatured dermis, the skin tissues of the deep partial-thickness burn rats were collected at different time points after burn creation and stained with hematoxylin and eosin (HE). Three days following burn creation, skin tissues showed pathological characteristics of a deep partial-thickness burn wound including nucleus pyknosis of the epidermal and follicular epithelial cells, disintegration of the sebaceous gland, and swelling and fusion of collagen (Fig 1A). Next, the expression of miR-23b in the denatured dermis was measured at different recovery time points after burn creation (1, 3, 5, and 7 days) by RT-PCR. As shown in Fig 1B, miR-23b expression demonstrated a dynamic alteration during the recovery of denatured dermis. Compared with that of normal skin, miR-23b expression significantly decreased in denatured dermis, with the greatest inhibitory rate of 81% after three days, but then gradually increased three days post-burn.

Bottom Line: MicroRNAs (miRNA) are small noncoding RNAs and regulate normal physiology as well as disease development.In addition, miR-23b modulated denatured dermis by activating the Notch1 and TGF-β signaling pathways.Our findings suggest that downregulation of miR-23b contributes to the recovery of denatured dermis, which may be valuable for treatment of skin burns.

View Article: PubMed Central - PubMed

Affiliation: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

ABSTRACT

Background: Skin grafting with the preservation of denatured dermis is a novel strategy for the treatment of burn-injured skin. Denatured dermis has the ability to restore to the morphology and function of normal skin, but the underlying molecular mechanism is elusive. MicroRNAs (miRNA) are small noncoding RNAs and regulate normal physiology as well as disease development. In this study, we assessed the potential role of miRNA-23b (miR-23b) in the regulation of cell proliferation and migration of heat-denatured fibroblasts and identified the underlying mechanism.

Methods: The expression of miR-23b in denatured dermis and heat-denatured fibroblasts was detected by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-23b on cell proliferation and migration of heat-denatured fibroblasts were assessed by transient transfection of miR-23b mimics and inhibitor. The target gene of miR-23b and the downstream pathway were further investigated.

Results: miR-23b was downregulated in denatured dermis and heat-denatured fibroblasts. Downregulation of miR-23b dramatically promoted the proliferation and migration of heat-denatured fibroblasts. Subsequent analyses demonstrated that Smad3 was a direct and functional target of miR-23b in heat-denatured fibroblasts, which was validated by the dual luciferase reporter assay. Moreover, immunohistochemistry analysis showed that denatured dermis from rats displayed enhanced staining of Smad3. In addition, miR-23b modulated denatured dermis by activating the Notch1 and TGF-β signaling pathways.

Conclusions: Our findings suggest that downregulation of miR-23b contributes to the recovery of denatured dermis, which may be valuable for treatment of skin burns.

No MeSH data available.


Related in: MedlinePlus