Objective To provide theoretical evidence for clinical application of the epidermal stem cells after an investigation on changes of the epidermal stem cells during the survival process after the fullthickness skin autograft. Methods On the backs of 42 Wistar rats, orthotopic transplantation models (1.5 cm×1.5 cm) of the fullthickness skin autograft were made. According to the time of the specimen taking, at 1, 3, 5, 7, 14, 21 and 30 days after operation, the rats were randomly divided in 7 groups (Groups 1-7). Specimens taken in each group before operation were used as controls. At each time point, the gross observation was made on the transplanted skin flaps, from which the skin tissues were harvested at each time point before and after operation. The routine pathological and the immunohistochemical examinations were performed on the specimens, which were stained by HE and were observed for immunohistochemical changes and the changes in the cells positive for integrinβ-1 and p63. Results All the fullthickness skin autografts survived 3 days after operation except the skin autograft in 1 rat in both Group 5 and Group 6, which was infected around the transplanted skin flap. In Groups 1-4, cell edema, inflammatory cell infiltration, and increased fibrocytes were observed. In Groups 5-7, the maturity degree of the epithelial cells became higher and higher, and the fibrocyte proportion was lowered. In each group the cell positivity rate for integrin β1 was lower than the cell positivity rate for p63. The positive cells were arranged in disorder, distributed into the layers of the epidermis and gradually concentrated in the basal layer of the epidermis and the bulge of the folliculus pili. The positive cells were also found in the other layers of the epidermis.The positive cells were gradually decreased in number, and reached the lowest level in Group 2. There was a significant difference in the above variables in Groups 1,2,3,5,6 and 7 between before and after operations (P＜0.05). Conclusion During the survival process of the fullthickness skin autograft, the proportion of theepidermal stem cells is gradually decreased at first; Then, the proportion isgradually increased, even beyond the normal level; finally, the proportion is decreased again. The distribution of the epidermal stem cells appear in disorder, almost distributed in the layers of the epidermis; finally, the almost normal distribution can be found.
Abstract: Objective To observe the expression of integrinlinked kinase (ILK) and matrix metalloproteinases9 (MMP9) in human nonsmall cell lung cancer (NSCLC) and investigate the correlation of ILK and MMP9 expression with the prognosis of NSCLC. Methods The expression of ILK and MMP9 in 75 specimens of NSCLC resected from January 2002 to January 2004 were detected by immunohistochemistry. According to the median of integral optical density (IOD), all patients were divided into the high or low ILK expression group and the high or low MMP-9 expression group. The relativity of ILK and MMP9 was determined, and the relationship of survival time with clinical features including expression of ILK and MMP-9 was compared by Logrank test. Results Both ILK and MMP-9 were expressed in NSCLC specimens. The expression between ILK and MMP-9 was positively correlated in 75 patients of our group (r=0.79, Plt;0.05). Patients with lower expression of ILK and MMP9 had a significantly longer survival time than those with higher expression of ILK and MMP-9 in the postoperative followup (χ2=15.067,14301,Plt;0.05). The survival time was not correlated with sex,age,smoking history or pathological type(χ2=0450,0078, 1.460, 1.623，Pgt;0.05), while tumor diameter, lymph node metastasis, TNM stage, the expression of ILK and MMP-9 significantly influenced the survival time (χ2=3.963, 15.169,20.529, 15.067，14.301，Plt;0.05). Conclusion The expression of ILK and MMP9 affects the prognosis of NSCLC. MMP-9 may advance infiltration and metastasis of tumor cells through ILK pathway. In summary, the expression of ILK and MMP9 may play an important role in the evaluation of prognosis for patients with NSCLC.
【Abstract】Objective To observe the changeable expressions of vascular endothelial growth factor (VEGF) and integrin β3 during the angiogenetic process of granulation tissue. Methods mRNA and protein of VEGF and integrin β3 in human normal subcutaneous tissue, proliferative granulation tissue and mature granulation tissue were observed by RT-PCR and immunohistochemistry staining. Results The expressions VEGF and integrin β3 were low in normal subcutaneous tissue and were much higher in proliferative granulation tissue. When the granulation tissue was mature, the expression was decreased again. Conclusion VEGF and integrin β3 are important regulating factors in ngiogenesis.
Objective To review the role of integrin in nervous system injury and its repair, and to analyze the possible mechanisms. Methods Recent l iterature concerning integrin and its role in nervous system injury was reviewed and analyzed. Results Integrin and its related signall ing pathway were involved in nervous system injury, especially hypoxicischemic nervous injury, and their repair processes. Conclusion Intervention of integrin signall ing pathway would be a potential strategy to treat nervous system injury, especially hypoxic-ischemic nervous injury.
Integrins is a family of multi-functional cell-adhesion molecules, heterodimeric receptors that connect extracellular matrix to actin cytoskeleton in the cell cortex, thus regulating various physiological and pathological processes. Risuteganib (Luminate?) is a novel broad-spectrum integrin inhibitor. Based on multiple biological functions of anti-angiogenesis, vitreolysis, and neuroprotection, risuteganib is hopeful in treating several fundus diseases such as diabetic macular edema, vitreomacular traction, and non-exudative age-related macular degeneration. By far, risuteganib has successfully met the endpoints for three phase 2 studies and is preparing to enter the phase 3 of diabetic macular edema clinical trials. Overall the risuteganib is safe with no serious ocular or systemic adverse events. Given the unique mechanism of action and longer duration of efficacy, intravitreal injection of risuteganib has the potential to serve as a primary therapy, or adjunctive therapy to anti-VEGF agents.
OBJECTIVE: To study the expression of type I collagen and its receptor system-integrin alpha 2 beta 1 in different passages of osteoblasts. METHODS: The expression of type I collagen and integrin alpha 2 beta 1 in the primary, sixth and fifteenth passage of osteoblasts were detected by S-P immunohistological staining technique, and their mRNA expression by quantity RT-PCR technique. RESULTS: Type I collagen and integrin alpha 2 beta 1 were expressed in different passages of osteoblasts and there was no significant difference among three passages by immunohistological technique. Their mRNA expression was gradually decreased with subculture. CONCLUSION: Type I collagen promotes the adhesion and phenotype expression of osteoblasts through its receptor-integrin alpha 2 beta 1. The reductive expression of type I collagen-receptor system will decline the phenotype of osteoblasts.
Objective To observe whether Cyclo-RGDfK (Arg-Gly-Asp-D-Phe-Lys) could enhance the adhesion of myofibroblast to decellularized scaffolds and upregulate the expression of Integrin αVβ3 gene. Methods Myofibroblast from the rat thoracic aorta was acquired by primary cell culture. The expression of Vimentin and α-smooth muscle actin(α-SMA) has been detected by immunoflurescent labeling. Decellularized valves have been randomly divided into three groups (each n=7). Group A (blank control): valves do not receive any pretreatment; Group B: valves reacted with linking agent NEthylN(3dimethylaminopropyl)carbodiimide hydrochloride (EDC) for 36 hours before being seeded; Experimental group: Cyclo-RGD peptide has been covalently immobilized onto the surface of scaffolds by linking agent EDC. The fifth generation of myofibroblast has been planted on the scaffolds of each group. The adhesion of myofibroblast to the scaffolds was evaluated by HE staining and electron scanning microscope. The expression of Integrin αVβ3 was quantified by halfquantitative reverse transcriptionpolymerase china reaction (RT-PCR). Results We can see that myofibroblast has exhibited b positive staining for Vimentin and α-SMA. Besides, it has been shown that the expression of Integrin αVβ3 was much higher in the experimental group than that of the group A and group B(Plt;0.05). There was no statistically difference in group A and group B (P=0.900). Conclusion RGD pretreatment does enhance the adhesive efficiency of seeding cells to the scaffolds and this effect may be related to the upregulation of Integrin αVβ3.
ObjectiveTo investigate the relationships between the expression of integrin β1 and activated cells in a partial-thickness articular cartilage injury model of adult rats.
MethodForty-five male Sprague Dawley rats (aged 10 weeks and weighing 300-400 g) were randomly divided into operated group (n=15) , sham-operated group (n=15) , and control group (n=15) . Partial-thickness articular cartilage injury model was made by scarification in operated group, direct suture after opening of the knee joint was performed in sham-operated group, and no operation was done in control group. Five rats were sacrificed at 1, 7, and 14 days after operation respectively for macroscopic evaluation, HE staining, Safranin O staining, CD105, BrdU, CD105/integrin β1 immunofluorescence and double labeling staining. The histological score of HE staining, gray value of Safranin O staining and CD105-positive cells count were compared among groups at each time point.
ResultsMacroscopic evaluation showed chondromalacia and cartilage fibrosis around the linear injury with aggravating tendency with time in operated group, but no chondromalacia and cartilage fibrosis in sham-operated and control groups. HE staining demonstrated a number of activated cells accumulating around the linear injury with nonuniform distribution in operated group, and uniform size and distribution in sham-operated and control groups. The histological scores at each time point in operated group were significantly higher than those in sham-operated group and control group (P<0.05) , but no significant difference was found between different time points in 3 groups (P>0.05) . Safranin O staining was nonuniform with hypochromasia around linear injury in operated group, but the staining was uniform in sham-operated group and control group. Gray value of Safranin O staining had no significant difference among groups and among different time points in the same group (P>0.05) . BrdU-positive and CD105-positive cells distributed unevenly around the linear injury in operated group, uniform distribution was observed in sham-operated group and control group. CD105-positive cells count in operated group was significantly higher than those in sham-operated group and control group at each time point (P<0.05) ; CD105-positive cells increased significantly with time in operated group (P<0.05) . CD105/integrinβ1-positive cells were observed around the linear injury in operated group, but was not observed in sham-operated group and control group.
ConclusionsThe partial-thickness articular cartilage injury model is successfully established in rats, and cartilage injury could not be repaired completely in the model. The activated cells aggregation around the linear injury can be observed, but there is no obvious relationships between activated cells and cartilage matrix. These activated cells are in proliferation and could express both CD105 and integrin β1.
Objective To observe the effect of epidermal growth factor (EGF) on integrin alpha;5 expression and its influence on human retinal pigment epithelium (RPE) cells.Methods Human RPE cells were treated in vitro with 0.1,1.0,10.0,20.0 and 100.0 ng/ml of EGF, the mRNA and protein of integrin alpha;5 was measured by reverse transcription polymerase chain reaction（RT-PCR）and flow cytometry. Human RPE cells were cultured under 4 conditions including DMEM/F12,DMEM/F12+10 ng/ml EGF, DMEM/F12+10 ng/ml EGF+rabbit antihuman integrin alpha;5 antibody (1∶100)，DMEM/F12+10 ng/ml EGF+rabbit antihuman vimentin antibody (1∶100), and their proliferation and migration were measured by methylthiazole tetrazolium（MTT）and Boyden chamber.Results The integrin alpha;5 mRNA level of human RPE cells was not changed after 12 hours of EGF stimulation (F=0.618, P=0.687), however it was induced in a dosedependent manner after 24 and 48 hours of EGF stimulation (F=465.303, 212.340; P=0.000,0.000).The protein level of integrinalpha;5 was higher in 10 ng/ml EGF stimulation compared with the control group and 0.1 ng/ml group（P＜0.01）.MTT and Boyden chamber showed that the integrin alpha;5 expression increased the proliferation and migration of human RPE cells. Conclusion EGF can induce integrin alpha;5 expression,thus increase the proliferation and migration of human RPE cells.
【Abstract】Objective To introduce the current research status, value and development future of Arg-Gly-Asp (RGD) peptides in diagnosis and treatment of neoplasms. Methods The current literatures on advances about RGD peptides in diagnosis and treatment of neoplasms were reviewed. Results RGD peptides, specificly recognizing and combining with integrin receptors, exist in extracellular matrix (ECM) of many kinds of organisms. After combining with integrin receptors, extrinsic RGD peptides can prevent tumor cells from adhering to ECM and migrating as the competitive inhibitor of intrinsic RGD peptides, suppress agiogenesis and induce tumor cells apoptosis, showing potential value of tumor specific imaging by targetal labelling neoplasms and treating tumors combining with other methods.Conclusion RGD peptides may be a new drug for diagnosis and treatment of neoplasms.
