In re-cent 20 years, the development of cell biology technology has promoted the research of keloid. Keloid fibroblasts (KFbs) are the main effector cells in keloid, which are closely related to the occurrence and development of keloid. It is significantly different in terms of biological characteristics and gene expression between KFbs and normal fibroblasts. This articles reviews the characteristics of KFbs from multiple perspectives, describing its biological character- istics in details including microstructures, metabolic character- istics, and proliferation properties, and introducing the main characteristics of heterogeneity and genomics of KFbs. The further research on KFbs will help to elucidate the pathogenesis of keloids and provide valuable strategies for the prevention and treatment of keloids.
Fibroblasts/metabolism* ; Humans ; Keloid/pathology*

OBJECTIVETo study the expression of alpha5beta1 integrin in the abnormal scars and its role and significance in the formation and development of abnormal scars.

METHODSThe expression of alpha5beta1 integrin was observed in hypertrophic scar (15 samples), keloid (15 samples) and normal skin (10 samples) with SP immunohistochemical method and colloidal gold immuno-electron microscopic technique. The data were semi-quantitatively analyzed.

RESULTSThe expression levels of alpha5beta1 integrin in the fibroblasts of keloids and hypertrophic scars were higher than normal skin; the expression of alpha5beta1 integrin in the fibroblasts of keloids was higher than hypertrophic scars (P < 0.01).

CONCLUSIONThe alpha5beta1 integrin appears to have close relation to the formation and development of abnormal scars. To find a way to decrease the expression level of alpha5beta1 integrin in fibroblasts may be a new approach to inhibit scar hypertrophy.

Cicatrix ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Integrin alpha5beta1 ; analysis ; metabolism ; Keloid ; metabolism ; pathology ; Microscopy, Immunoelectron ; Skin ; chemistry ; pathology ; ultrastructure

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 investigate the abnormalities of human epiderm in keloids and hypertrophic scars.

METHODSBiopsies from ten untreated keloids (duration of disease 3 - 30 years) and ten hypertrophic scars (duration of disease 6 - 10 months) and five normal adult skin specimens. Total RNA was isolated from normal adult skin. A cDNA fragment (base 5941 - 6481 bp) of the full-length human Tenascin-C cDNA was synthesized by polymerase chain reaction and subcloned in pGEM-T-easy. Dioxigen-labeled anti-sense and sense probes were synthesized by using a Sp6/T7 in vitro RNA synthesis kit in the present of Dig-UTP. In situ hybridization was performed on 4% paraformaldehyde-fixed and wax-embedded sections of keloids and hypertrophic scars. NBT-NCIP was used in color detection. Immunohistochemical procedure. The sections were incubated with antibodies (anti-Tenascin-C, anti-CK-16 and anti-Ki-67). Ultrasensitive Streptavidin Peroxidase staining was performed following established procedures.

RESULTSThe study show that the proliferation of epidermal keratinocytes in keloids and hypertrophic scars is very clear. The expressions of Tenascin-C mRNA in keloids epidermal keratinocytes markedly increased in contrast with epidermal keratinocytes of hypertrophic scars and adult skin. The CK-16 and Ki-67 stainings significantly enhanced in the epidermal keratinocytes of keloids and hypertrophic scars.

CONCLUSIONSThe different expressions of Tenascin-C, CK-16 and Ki-67 among normal adult skin, keloids and hypertrophic scars show the abnormalities of epidermal keratinocytes proliferation and differentiation in keloids and hypertrophic scars.

Cicatrix, Hypertrophic ; metabolism ; pathology ; Epidermis ; metabolism ; pathology ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; In Situ Hybridization ; Keloid ; metabolism ; pathology ; Keratins ; genetics ; metabolism ; Ki-67 Antigen ; genetics ; metabolism ; Male ; Tenascin ; genetics ; metabolism

OBJECTIVETo study the expressions of Notch1-4 gene in human keloid-derived mesenchymal-like stem cells, and to explore the Notch signaling pathway's role in the formation of keloid.

METHODSKeloid samples were collected to harvest human keloid-derived mesenchymal-like stem cells through two-step enzymatic dissociation method. By flow cytometry, cell phenotype of primary and P3 generation were analyzed. By immunocytochemistry, the expressions of Oct4, vimentin and CK19 were examined. Keloid-derived mesenchymal-like stem cells were induced into osteoblasts in vitro and calcium deposition was detected by Alizarin red S stain. Realtime polymerase chain reaction (RT-PCR) was used to detect the expressions of Notch1-4 mRNA in keloid-derived mesenchymal-like stem cells.

RESULTSFlow cytometry showed that keloid-derived mesenchymal-like stem cells of primary and P3 generation highly expressed CD29, CD44, CD90 from the typical MSC phenotype marker, but they failed to express HSC phenotype markers, such as CD34 and CD45. The results of immunocytochemistry showed that Oct4 from pluripotent stem cell markers and vimentin from mesenchymal cell markers was positive and CK19 from epithelial cell markers was negative. After induced differentiation into osteoblasts in vitro after 21 day, calcium nodules could be seen clearly; Notch1-4 gene were expressed in keloid-derived mesenchymal-like stem cells through RT-PCR. The relative quantitative of Notch2, Notch3 gene were higher than Notch1, Notch4 gene (P < 0.05).

CONCLUSIONSThe expression difference of different subtypes from Notch gene in human keloid-derived mesenchymal-like stem ceils may be related to self-renewal, proliferation, differentiation, and participate in the formation of keloid.

Adolescent ; Cells, Cultured ; Child ; Female ; Humans ; Keloid ; metabolism ; pathology ; Male ; Mesenchymal Stromal Cells ; metabolism ; Receptors, Notch ; metabolism

OBJECTIVETo investigate the expression and distribution of mast cell tryptase (MCT) in scar, and to discuss the different MCT gene expression in keloid, hypertrophic scar and normal skin.

METHODS20 samples of keloid, 20 samples of hypertrophic scar and 20 samples of normal skin were collected. The distribution of MCT was investigated by immunofluorescence histochemistry, and the MCT mRNA expression was detected by Relative Quantification real-time fluorescent PCR.

RESULTSMCT gene was mainly located in the collagen fiber bundles of the scar, especially in the superficial layer of scar. MCT mRNA expression was significantly higher in keloid than that in hypertrophic scar and normal skin (P < 0.01). Averagely, the MCT gene expression in keloid was 2.5 times and 5.4 times of that in hypertrophic scar and normal skin.

CONCLUSIONSMCT gene may play a role in the pathogenesis of scar.

Adolescent ; Adult ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Humans ; Keloid ; metabolism ; pathology ; RNA, Messenger ; genetics ; Skin ; metabolism ; pathology ; Tryptases ; genetics ; metabolism ; Young Adult

OBJECTIVETo probe into periostin's role in the pathological mechanism of hyperplasic scars, by examining the expression of periostin in hyperplasic scar tissues. To investigate the correlations between periostin and TGF-beta1, TGF-beta R I, TGF-beta R II.

METHODSRT-PCR was used to assess the mRNA expression levels of TGF-beta1, TGF-beta R I, TGF-beta R II in three kinds of tissues, which are keloid (K), hypertrophic scar (HS) and normal skin (SK). The protein expression of periostin was measured with Western blotting.

RESULTSThe mRNA level of periostin in K was higher than that in SK. The mRNA expression of TGF-beta1 in K was higher than that in HS and SK. The mRNA level of TGF-beta R I in K was higher than that in HS and SK. The significances above all was at P < 0.01. The protein expression level of periostin in HS increased, compared with that in SK (P < 0.05). Periostin was related to TGF-beta1 positively (P <0.01).

CONCLUSIONSThe periostin's expression is increased in keloids. Periostin is a cicatrix specific gene. Periostin appears to play an important role in the formation of keloids, which is related to TGF-beta1 closely.

Adult ; Cell Adhesion Molecules ; metabolism ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Female ; Humans ; Keloid ; metabolism ; pathology ; Male ; Receptors, Transforming Growth Factor beta ; metabolism ; Transforming Growth Factor beta1 ; metabolism

Keloids are a common type of pathological scar as a result of skin healing, which are extremely difficult to prevent and treat without recurrence. The pathological mechanism of keloids is the excessive proliferation of fibroblasts, which synthesize more extracellular matrices (ECMs), including type I/III collagen (COL-1/3), mucopolysaccharides, connective tissue growth factor (CTGF, also known as cellular communication network factor 2 (CCN2)), and fibronectin (FN) in scar tissue, mostly through the abnormal activation of transforming growth factor-‍β (TGF-‍β)/Smads pathway (Finnson et al., 2013; Song et al., 2018). Genetic factors, including race and skin tone, are considered to contribute to keloid formation. The reported incidence of keloids in black people is as high as 16%, whereas white people are less affected. The prevalence ratio of colored people to white people is 5:1‍‍-‍‍15:1 (Rockwell et al., 1989; LaRanger et al., 2019). In addition, keloids have not been reported in albinism patients of any race, and those with darker skin in the same race are more likely to develop this disease (LaRanger et al., 2019). Skin melanocyte activity is significantly different among people with different skin tones. The more active the melanocyte function, the more melanin is produced and the darker the skin. Similarly, in the same individual, the incidence of keloids increases during periods when melanocytes are active, such as adolescence and pregnancy. Keloids rarely appear in areas where melanocytes synthesize less melanin, such as in the palms and soles. Thus, the formation of keloids seems to be closely related to melanocyte activity.
Adolescent ; Cells, Cultured ; Exosomes/metabolism* ; Fibroblasts/metabolism* ; Humans ; Keloid/pathology* ; Melanins/metabolism* ; Melanocytes/pathology* ; Pilot Projects ; Skin/metabolism* ; Transforming Growth Factor beta/metabolism*

OBJECTIVETo investigate the effects of wild type p16 gene on the proliferation and metabolism of human keloid fibroblasts.

METHODSEukaryotic expression vector pcDNA3-p16 was constructed and imported into KFb by gene transfection mediated by liposome. And the positive clones were screened by G418. The transfected and untransfected KFbs were stained by Immunocytochemical method. The expression of p16 protein was observed. The changes of the proliferation and DNA synthesis of KFb before and after transfection were observed and compared by drafting cell growth curve and by (3)H-TdR incorporation method.

RESULTSThe recombinant vector pcDNA3-p16 was successfully constructed and identified by enzyme digestion. The positive clones were identified by G418 selection for 10 days from transfected KFb and with p16 protein expression. The growth rate of transfected KFb slowed down obviously and its DNA synthesis decreased significantly (P < 0.05) when compared with those of normal KFb.

CONCLUSIONp16 gene might inhibit the growth and DNA synthesis of KFb.

Cell Proliferation ; Cells, Cultured ; DNA ; biosynthesis ; Fibroblasts ; metabolism ; pathology ; Genes, p16 ; Genetic Therapy ; Humans ; Keloid ; genetics ; pathology ; Transfection

OBJECTIVE: To investigate the relationshion between the angiogenesis of different kinds of scar and expression of HO-1. METHODS: The expression of heme oxygenase-1 and vessel counted by CD34 of biopsies from different kinds of scars such as hypertrophic scar, keloid, surgical scar and normal skin of 24 cases was valued by immunochemical method, and the relationship was compared between them. RESULTS: The vessel count of hypertrophic scar, keloid was significantly abundant compared with surgical scar or normal skin (P < 0.01). While the expression of HO-1 of hypertrophic scar, keloid was obviously higher than that in surgical scar or normal skin (P < 0.01), decreased from hypertrophic scar, keloid, surgical scar to normal skin. There existed a positive correlation between vessel count and the expression of HO-1 (r = 0. 761, P < 0.01) as well as the number of fibroblastic cells (r = 0. 731, P < 0.01) in the study groups. CONCLUSION HO-1 might play a important role in the angiogenesis of scar formation. The cause of these changes may be local. Over angiogenesis is one symbol of pathological scar.
Adult ; Cicatrix ; metabolism ; pathology ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Female ; Heme Oxygenase-1 ; biosynthesis ; genetics ; Humans ; Keloid ; metabolism ; pathology ; Male ; Middle Aged ; Neovascularization, Pathologic ; Skin ; blood supply