OBJECTIVETo study the expression of P57(kip2) and Maspin in the pathological scar and their possible role in the pathogenesis of abnormal scars.

METHODSImmunohistochemistry integrated image analysis and reverse transcription polymerase chain reaction (RT-RCR) were performed to detect the expression of P57(kip2) and Maspin in hypertrophic scar, keloid, mature scar and normal skin. Statistics was used to analyze the datas.

RESULTSThe expression of P57(kip2) protein was fixed to fibroblast intranuclear in abnormal scar, and the expression of P57(kip2) protein and P57(kip2) mRNA decreased (P < 0.05). The expression of Maspin protein was fixed to fibroblast cytoplasm and intranuclear in abnormal scar, and the expression of Maspin protein and Maspin mRNA decrease, compared with that in normal group (P < 0.05). There was positive correlation between P57(kip2) protein and Maspin protein expression (P < 0.01).

CONCLUSIONSThe decreased expression of P57(kip2) and Maspin in abnormal scar shows that they are cicatrix-related genes. There is a positive relationship between the two genes. It may be one of the mechanisms of pathogenesis of abnormal scar. It makes effect through fibroblasts.

Cicatrix ; metabolism ; pathology ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p57 ; metabolism ; Fibroblasts ; metabolism ; Humans ; Serpins ; metabolism

OBJECTIVETo investigate the influence of substance P (SP) on the release of histamine in the human hypertrophic scar tissue, and to explore the prerequisite of their interaction.

METHODSTissue specimens of normal skin and hypertrophic scar from eight hospitalized patients were excised and cut into 0.5 to 1.0 mm3 pieces, and the histamine release by mast cell (MC) under the stimulation of different concentration of SP and calcium, as well as the different affect time of SP, were determined with fluorescence spectrometer. Then the histamine release rate was calculated.

RESULTSThere was obvious release of histamine when SP concentration was 1 x 10(-6) mol/L , and the release rate was (50.0 +/- 3.6) %, which was significantly higher than that by SP in the concentration of 0 mol/L [(44.0 +/- 3.2) %, P < 0.01]. Therefore it seemed to be dose-dependent. About 90% of histamine was released within 15 minutes of 5 x 10(-1) mol/L Substance P stimulation, and it was also time-dependent. The histamine release reached the peak when calcium concentration was 5 x 10(-3) mol/L, which seemed to be dose-dependent, but it decreased transiently when calcium concentration was 1 x 10(-3) mol/L. In all occasions, the influence of SP on the histamine release by MC in hypertrophic scar (HS) was markedly higher than that in normal skin (NS) (P < 0.01). Conclusion The influence of SP on the histamine release by MC in HS was markedly higher than that in NS, and it might be closely related to itching sensation and the formation of hypertrophic scar.

Child ; Child, Preschool ; Cicatrix, Hypertrophic ; metabolism ; Female ; Histamine ; metabolism ; Humans ; Male ; Skin ; metabolism ; Substance P ; pharmacology

OBJECTIVETo explore the role of collagen degradation and scar morphology and structure in the formation of hypertrophic scar.

METHODSSDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) plus collagen substrate electrophoresis, amino acid analysis and compound staining were employed to observe the collagenase activity within hypertrophic scar, collagen degradation and the tissue morphology of the scar.

RESULTSThere exhibited deranged collagen fibres within hypertrophic scar, and large amounts of acid mucopolysaccharide closely surrounded the collagen fibres. All these led to an obvious decrease in collagenase activity and reduction of collagen degradation.

CONCLUSIONThe decrease of collagen degradation and the formation of hypertrophic scar might be closely related to the decrease in collagenase activity and the inhibiting activity of acid mucopolysaccharide on collagenase.

Adolescent ; Adult ; Child ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Collagen ; metabolism ; Collagenases ; metabolism ; Female ; Humans ; Male

Objective: To explore the effect of microRNA(miR)-222 on cell proliferation and apoptosis of fibroblasts in hypertrophic scar (HS) and the underlying mechanisms. Methods: The expression of miR-222 in the HS and the normal skin tissues was detected by real-time RT-PCR. The HS fibroblasts were transfected with miR-222 mimic and miR-222 inhibitor respectively. The cell viability was tested with MTT assay, cell cycle distribution and apoptosis were detected with flow cytometry and the expression levels of proliferation, apoptosis and cell cycle related proteins were determined with Western blot. Direct target of miR-222 was evaluated by dual-luciferase reporter assay. Results: miR-222 was significantly up-regulated in HS tissues compared with normal skin tissues(P<0.05). Overexpression of miR-222 enhanced the cell viability of HS fibroblasts; increased mRNA and protein expressions of proliferating cell nuclear antigen (PCNA), collagen alpha-1 (Ⅰ) chain (Col1A1) and collagen alpha-1 (Ⅲ) chain (Col3A1); increased cell population in S phase and protein expressions of cyclin D1, cyclin E1 and cyclin-dependent kinases 1 (CDK1); inhibited cell apoptosis and reduced protein expressions of caspase-3/9. Overexpression of MMP1 attenuated the effects of miR-222 on the cell viability and apoptosis in fibroblasts, reduced expression levels of PCNA, cyclin D1 and the expression of caspase-3 was increased. Conclusion: miR-222 enhances cell proliferation and inhibits cell apoptosis of HS fibroblasts through negative regulation of MMP1, which suggests that miR-222 and MMP1 might be used as novel biomarkers and targets in diagnostic and therapeutic approaches for HS.
Apoptosis ; genetics ; Cell Proliferation ; genetics ; Cicatrix, Hypertrophic ; Fibroblasts ; Humans ; Matrix Metalloproteinase 1 ; metabolism ; MicroRNAs ; metabolism

Hypertrophic scar is a pathological repair result of excessive accumulation of extracellular matrix after skin damage, which affects the appearance and function of patients with varying degrees. The degree of scar formation is directly related to the strength of inflammatory reaction during wound healing, and excessive or prolonged inflammatory response increases the incidence of hypertrophic scars. Interleukin-6 (IL-6) is a pleiotropic cytokine that is involved in regulating the fibrotic network composed of fibroblasts, macrophages, keratinocytes, and vascular endothelial cells, and is closely related to the formation of hypertrophic scars. This article reviews the role of IL-6 and its signaling pathway in hypertrophic scar formation.
Cicatrix, Hypertrophic/pathology* ; Endothelial Cells/metabolism* ; Fibroblasts/metabolism* ; Humans ; Interleukin-6 ; Skin/pathology* ; Wound Healing/physiology*

Scarring, naturally induced by fibroblasts(Fb) during wound healing, is an essential process in response to repair damaged tissue. Excessive Fb proliferation which produces the excessive collagen deposition, including increased extracellular matrix synthesis or insufficient decomposition, typically contributes to hypertrophic scar(HS) formation. Although exact mechanisms of HS are not yet fully understood, it is generally believed that dysfunction of Fb and regulation of signal pathways play an important role in HS formation. Biologically, Fb function is affected by various factors such as cytokines, extracellular matrix and itself. In addition, modifications of miRNA, ceRNA, lncRNA, peptides and histones participate in HS formation by affecting the biological function of Fb. Despite the clinical importance, very few therapeutic modalities are available to prevent HS. To achieve this, a deeper characterization of Fb is required to identify mechanisms of HS. To the aspect of HS prevention and treatment, we review recent findings, concentrating on Fb function and collagen secretion. The objective of this article is to frame the current understanding, gain the deeper insights into Fb function, and provide the more comprehensive cognition and perspective for prevention and treatment of HS.
Humans ; Cicatrix, Hypertrophic/metabolism* ; Collagen/therapeutic use* ; Fibroblasts ; Signal Transduction ; Extracellular Matrix/metabolism*

OBJECTIVETo investigate the expression of tenascin-C (Tn-C) in keloid and hyperplastic scar (HS).

METHODSTissue samples were harvested from 10 patients with keloid and 10 with HS (6 - 10 months) and from the skin of 5 adult healthy volunteers. The expression of Tn-C in these samples was determined with immunohistochemistry method.

RESULTSThere was scarce expression of Tn-C in the skin tissue in adult healthy volunteers, and it was only present in the dermal papillae at the dermis epidermis conjunctions and partly in the blood vessels and skin appendages adjacent to the basement membrane. There was enhanced expression of Tn-C in the dermal scar tissue and skin appendages in both keloid and HS, especially in keloid, which exhibited a diffused pattern in the tissue. When compared with that in normal skin, the Tn-C expression in the normal skin adjacent to the keloid was enhanced markedly, but not in the normal skin near HS tissue.

CONCLUSIONThere was increased Tn-C expression in keloid and HS (6 - 10 months).

Cicatrix, Hypertrophic ; metabolism ; Female ; Humans ; Immunohistochemistry ; Keloid ; metabolism ; Male ; Skin ; chemistry ; Tenascin ; analysis

OBJECTIVETo investigate the expression of Tenascin-C mRNA in keloids and hypertrophic Total RNA was isolated from normal adult skin. A cDNA fragment (base 5941-6481bp) of the scars.

METHODSfull-length human Tenascin-C cDNA was synthesized by polymerase chain reaction and subcloned in pGEM-T-easy. Dioxygen-labeled anti-sense and sense probes were synthesized by using a Sp6/T7 RNA synthesis kit in the present of Dig-UTP in vitro. The samples were taken from keloids in 10, hypertrophic scars in 10 and normal adult skin in 5. The hybridization was performed with 4% paraformaldehyde-fixed and wax-embedded sections to detect the Tenascin-C mRNA.

RESULTSThe Tenascin-C mRNA was negative in the normal adult epidermis and weakly located in the fibroblasts of the papillary dermis and the epidermal adnexa. In all of the 10 keloid specimens, the Tenascin-C mRNA was positive throughout the epidermis and widely distributed in the dermis included in the fibroblasts, endothelial cells and epidermal adnexa. In the specimens of the 3 hypertrophic scars,the Tenascin-C mRNA was also positive in the epidermis, but in the other 7 cases, it became negative. In the dermis of the hypertrophic scar,the Tenascin-C mRNA was weaker than that in the keloid, but stronger than that in the normal skin.

CONCLUSIONSThe expression of Tenascin-C mRNA is markedly enhanced in the keloids.

Cicatrix, Hypertrophic ; genetics ; metabolism ; pathology ; Female ; Humans ; Keloid ; genetics ; metabolism ; pathology ; Male ; RNA, Messenger ; metabolism ; Tenascin ; genetics ; metabolism

OBJECTIVETo observe the effects of Genistein on TGF-beta1 expression and the intracellular free Ca2+ concentration in human hypertrophic scar fibroblasts, and to discuss the mechanism of the anti-fibrosis effect.

METHODSFibroblasts were derived from human hypertrophic scar tissue and cultured in vitro. Genistein in different concentrations (25, 50, 100 micromol/L) was administrated to the fibroblasts, respectively. After 48 hours of co-culture, the expression of TGF-beta1 mRNA and protein were examined by RT-PCR and Western-Blot assay respectively. The intracellular free Ca2+ concentration in hypertrophic scar fibroblasts pretreated by Genistein was determined by laser confocal scanning microscopy with or without the stimulation of bFGF.

RESULTSGenistein inhibited the expression of TGF-beta1 in hypertrophic scar fibroblasts on a concentration-dependent manner. bFGF significantly elevated the intracellular free Ca2+ concentration, however its stimulating effect was remarkably alleviated when the fibroblasts were pre-treated by Genistein.

CONCLUSIONSGenistein can reduce the expression of TGF-beta1 and block the accumulation of intracellular free calcium induced by growth factors. It maybe one of the possible mechanisms of Genistein's antifibrosis effect.

Calcium ; analysis ; Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Genistein ; pharmacology ; Humans ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo establish and optimize the two dimensional gel electrophoresis (2-DE) map of epidermal cells separated from the hypertrophic scar tissues so as to explore the function of the non cultured epidermal cells during the course of the formation of hypertrophic scar.

METHODSTo separate the epidermal cells from the scar tissues, the scar epidermis was digested with Dispase II and trypsin. The total protein of the cells was then extracted and separated with 2-DE and visualized with silver stain. Spots detection and matching were performed with Melaine 3.0 gels analyzing software. The results were then compared with the normal epidermal cells' 2-DE map coming from the Danish Center for Human Genome Research' s 2-DE PAGE Databases.

RESULTSNearly more than 600 protein spots were identified in the final optimized 2-DE map. We found out 24 differentially expressed proteins by comparing the difference in composition, shape or density of all the spots. In the 24 proteins, there are 8 up-regulated ones, 9 down-regulated ones, 4 disappeared ones and 3 newly founded ones.

CONCLUSIONSThe method of digesting the epidermis with Dispase II and trypsin to separate the epidermal cells to establish the 2-DE map is feasible and it made the further study on hypertrophic scar proteomics possible. The 24 differentially expressed proteins revealed that epidermal cells might play a role in the formation of hypertrophic scar.

Cell Line ; Child ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Electrophoresis, Gel, Two-Dimensional ; methods ; Epidermis ; metabolism ; Humans ; Proteome ; metabolism