Drug-induced gingival overgrowth (DIGO) is characterized by fibrous gingival hyperplasia and increased gingival volume. DIGO is histologically associated with proliferation of cells and deposition of extracellular matrices, particularly collagen. Integrin α2β1 is related to collagen phagocytosis and involved in the occurrence and progression of DIGO. This paper reviews the progress of research on the relationship between integrin α2β1 and DIGO.
Collagen ; Gingiva ; Gingival Overgrowth ; Humans ; Integrin alpha2beta1 ; Phagocytosis

OBJECTIVETo study the effect of integrin alpha2beta1 on invasion and migration of SK-N-SH neuroblastoma cells.

METHODSNeuroblastoma SK-N-SH cell line was cultured in the modified eagle's medium. The effects of monoclonal antibodies to integrin alpha2 and integrin beta1 on migration and invasion were measured by inclined test and polycarbonate filters incorporated in modified Transwell chambers respectively. The migration and invasion cells were stained with Gimsa staining and counted under a 200 multiplied microscope. The blocking rate of migration and invasion of cells was calculated.

RESULTSThe number of migrated SK-N-SH cells in the anti-alpha2 and anti-beta1 treatment groups (50.9+/-10.5 and 54.3+/-9.0 respectively) was significantly less than that in the control group without monoclonal antibody treatment (98.1+/-7.4) (P<0.01), with a blocking rate of cell migration of 48.1% and 44.5% respectively. The invasion to matrigel of SK-N-SH cells exposed monoclonal antibodies to integrin alpha2 and integrin beta1 was significantly blocked compared with the control SK-N-SH cells, with the number of invasion cells in the anti-alpha2 and anti-beta1 treatment groups of 25.3 +/- 4.4 and 18.8 +/- 3.9 respectively vs 41.5 +/- 4.8 in the control group (P<0.01). The blocking rate of cell invasion in the anti-alpha2 and anti-beta1 treatment groups was 39.0% and 54.7% respectively.

CONCLUSIONSIntegrin alpha2beta1 may promote migration and invasion of neuroblastoma cells.

Cell Line, Tumor ; Cell Movement ; Collagen Type I ; physiology ; Humans ; Integrin alpha2beta1 ; physiology ; Neoplasm Invasiveness ; Neuroblastoma ; pathology

Stem cells are characterized by self-renewing, multipotent differentiation, and high proliferation and receiving more and more attention for their roles in the development and management of various diseases. There are epithelial stem cells and mesenchymal stem cells in the prostate. The markers of the epithelial stem cells include cytokeratin, stem cell antigen-1, and integrins alpha2beta1, CD49f, CD133, CD117, and CD44. The markers of the mesenchymal stem cells include CD30, CD44, CD133, neuron-specific enolase, and vascular endothelial growth factor receptor-1. Prostate stem cells are involved in the development and treatment of prostatic diseases. This review focuses on the latest progress in the studies of prostate stem cells.
Antigens, CD ; Biomarkers ; Cell Differentiation ; Humans ; Integrin alpha2beta1 ; Male ; Prostate ; cytology ; Stem Cells ; chemistry ; cytology ; Vascular Endothelial Growth Factor A

Anodic spark deposition method(ASD) surface treated titanium implant possesses a considerable osteoconductive potential that promoting a high level of implant osseointegration in normal bone. The purpose of this study was to observe the ASD implant's osseointegration in the osteoporosis-induced animal model. Twenty four rats, 10 weeks of age, were ovarectomized and 5 weeks later divided into two groups : ASD implant group and control implant group. Titanium screw implants (diameter; 2.0 mm, length, 3.5 mm; pitch-height, 0.4 mm) were designed for this study. Experimental implants were ASD treated and no treatment on control implants. ASD implants and control implants were placed in to left tibiae of rats. The rats were sacrificed at different time interval(1, 2, 4 and 8 weeks after implantation) for histopathologic observation and immunohisto -chemistrical observation, with collagen type I, fibronectin, integrin alpha2beta1 and integrin alpha5beta1 antibodies. The results obtained from this study were as follow: 1. Histopathologic findings, overall tissue response and the pattern of bone formation in both groups were similar. In ASD group, more newly formed bone was seen at 1 week and 2weeks than control group. 2. The levels of type I collagen and fibronectin expression were the most abundant at 2weeks and decreased gradually in both groups. Fibronectin and type I collagen expression in ASD group were stronger than control group but no significance. 3. The levels of integrin alpha2beta1 and Integrin alpha5beta1 expression were most abundant at 2 weeks and decreased gradually in both groups. No significant difference was observed in both groups. From this results, anodic oxidized titanium implants were more advantages in early stage of bone formation than control group, but have no significance in tissue responses and late bone formations. It could be stated that although anodic oxidized titanium implant possesses considerable osteoconductive potential but in osteoporotic bone condition dental implant procedure should performed after improving or treating the osteoporotic bone condition.
Animals ; Antibodies ; Collagen Type I ; Dental Implants ; Fibronectins ; Implants, Experimental ; Integrin alpha2beta1 ; Integrin alpha5beta1 ; Models, Animal ; Osseointegration ; Osteogenesis ; Osteoporosis ; Rats ; Tibia ; Titanium

OBJECTIVETo explore the molecular mechanisms of Glanzmann thrombasthenia caused by alpha II b L721R and Q860X compound heterozygous mutation.

METHODSAll exons and exon-intron boundaries of alpha II b and beta3 gene were amplified by PCR and analyzed by direct DNA sequencing. Gene polymorphisms were excluded by direct DNA sequencing. Alpha II b L721R and Q860X mutants expressing vectors were constructed by in vitro site-directed mutagenesis. The expression of alpha II b L721R and Q860X mutants on transfected cell membrane were analyzed by flow cytometry and the whole expression level was confirmed by Western blot. The subcellular localizations of alpha II b L721R and Q860X mutants were determined by immunofluorescent confocal scanning microscopy.

RESULTSThe alpha II b compound heterozygous mutations, T2255G (L721R) and C2671T (Q860X), were identified in the proband, the former being inherited from the maternal side and the latter the paternal side. The 293T cells cotransfected with mutated alpha II b L721R and wild-type beta3 expression plasmids expressed 2.1% of normal amount of alpha II b on the cell surface as shown by FACS, in contrast to 31.9% of normal amount of alpha II b on the cells cotransfected with cDNAs of mutated alpha II b Q860X and wildtype beta3 expression plasmids. Western blot of the cell lysates showed no detectable mature alpha II b in cells lysates with L721R mutant. While, truncated alpha II b protein was detected in cell lystes with Q860X mutant. Immunofluorescence studies demonstrated that both L721R and Q860X mutant pro-alpha II bbeta33 complex colocalized in endoplasmic reticulum, but a little in Golgi.

CONCLUSIONSThe L721R and Q860X mutations of alpha II b prevent transport of the pro-alpha II bbeta3 complex from the endoplasmic reticulum to the Golgi, hindering its maturation and surface expression. The impaired alpha II bbeta3 transport is responsible for the thrombasthenia.

Animals ; CHO Cells ; Child, Preschool ; Cricetinae ; Cricetulus ; Female ; Genetic Vectors ; Heterozygote ; Humans ; Integrin alpha2beta1 ; genetics ; metabolism ; Mutagenesis, Site-Directed ; Mutation ; Thrombasthenia ; genetics ; Transfection

OBJECTIVETo investigate the distribution of epidermal stem cells (ESCs) in different degrees of burn wounds in scalded rats.

METHODSThirty-two Sprague-Dawley (SD) rats were employed in the study. First degree (I), shallow (shallow II) and deep partial thickness (deep II) and full thickness burn wounds (III) were created on the rat skin. Burn wound samples were harvested at 24 postburn hours (PBHs) from all the wounds and were processed to tissue slices. The tissue slices were stained by immunohistochemistry technique. The expression and distribution of ESCs in different degrees of burn wounds were observed with integrins alpha 2 beta 1 and keratin 10 (K10) as first antibodies.

RESULTSK10 positive cells were found to distribute in the strata spinosum, granulosum and lucidum in the first degree burn wound (I) with large amounts of integrins alpha 2 beta 1 positive cells in the residual basal layer and skin appendages (hair follicles) in shallow partial thickness burn wound (shallow II degree), and there were less integrins alpha 2 beta 1 positive cells in the remaining skin appendages in deep dermis in deep partial thickness burn wound (deep II degree). Finally, integrins alpha 2 beta 1 positive cells were sparsely found in the III degree burn wound.

CONCLUSIONThe distribution of ESCs in burn wounds was closely related to the depth of burn wound. The residual ESCs might be the origin of burn wound regeneration and reepithelization.

Animals ; Burns ; metabolism ; pathology ; Female ; Immunohistochemistry ; Integrin alpha2beta1 ; analysis ; Keratin-10 ; Keratins ; analysis ; Male ; Rats ; Rats, Sprague-Dawley ; Stem Cells ; pathology

OBJECTIVETo study the effect of endogeneous gangliosides (Gls) on integrin alpha2beta1-mediated adhesion of neuroblastoma cells to collagen (Col).

METHODSNeuroblastoma SK-N-SH cell line was cultured in the modified eagle's medium with the presence of 10 mum D-threo-1-phenyl-2-decanolamino-3-morphinolin-1-propanol (D-PDMP), an inhibitor of glucosylceramide synthase. Flow cytometry was used to detect the expression of integrin alpha2beta1 in the cell line. The effects of Mg2(+) and monoclonal antibodies to integrin alpha2beta1 on the adhesion of the cell line to immobilized Col were observed. The adhesion cell number was measured with the BCA method and presented with absorptance A570.

RESULTSThere was a high expression of integrin alpha2beta1 in the SK-N-SH cell line without D-PDMP treatment. Endogenous Gls in the cells were almost depleted after 6-day exposure to D-PDMP, but the integrin alpha2beta1 expression was not significantly changed. 1 mmoL/L Mg2(+) treatment increased significantly the number of adhesion cells in the SK-N-SH cell line. The adhesion to Col of the SK-N-SH cells exposed to D-PDMP which Gls was depleted was significantly reduced compared with the control SK-N-SH cells treated with 1 mmoL/L Mg2(+) (A570: 0.33 +/- 0.016 vs 0.57 +/- 0.033; P < 0.01). After endogeneous Gls was added into the Gls-depleted SK-N-SH cells, the adhesion of the cells was restored (A570: 0.52 +/- 0.035). The adhesion of SK-N-SH cells was significantly blocked by anti-alpha2 and anti-beta1 monoclonal antibodies, with A570 of 0.31 +/- 0.018 and 0.36 +/- 0.021 respectively.

CONCLUSIONSEndogenous tumor Gls increases neuroblastoma cell adhesion to Col by regulating the function of integrin alpha2beta1, but has no effects on the integrin expression. It is suggested that tumor Gls may play a role in migration, invasion and metastasis of tumor cells.

Antibodies, Monoclonal ; immunology ; Cell Adhesion ; Cell Line, Tumor ; Collagen ; physiology ; Gangliosides ; physiology ; Humans ; Integrin alpha2beta1 ; physiology ; Magnesium ; pharmacology ; Morpholines ; pharmacology ; Neuroblastoma ; pathology

This study was aimed to further investigate the function of platelet collagen receptor-glycoprotein VI and to screen its specific inhibitor. The extracellular domain of platelet glycoprotein VI (GPVI) in E. coli was expressed by recombinant technology, the extracellular domain cDNA of GPVI was amplified from pBluescript KS(-)-GPVI plasmid by PCR. Proved by sequencing, the expression vector pET-20b(+)-GPVI was constructed, which was then transformed into E. coli (BL21(DE3)pLysS) and induced by IPTG. The recombinant GPVI was purified on Ni-NTA resin column and renatured in PBS containing GSH and GSSG. The anti-penta His McAb and anti-GPVI polyclonal antibody were used to identify the recombinant GPVI in Western blotting. Collagen binding test was conducted to investigate the biological activity of recombinant GPVI. The results showed that the recombinant GPVI was expressed in E. coli and successfully purified, which was confirmed to be similar to the native GPVI in Western blotting. The recombinant GPVI can bind the type I collagen in dose-dependent manner. In conclusion, the recombinant GPVI can be achieved in E. coli and restore its native characteristics after renaturation.
Blood Platelets ; metabolism ; Blotting, Western ; Escherichia coli ; genetics ; Humans ; Integrin alpha2beta1 ; Platelet Membrane Glycoproteins ; biosynthesis ; genetics ; Protein Binding ; Receptors, Collagen ; biosynthesis ; genetics ; Recombinant Proteins ; biosynthesis ; isolation & purification

OBJECTIVETo study the expressions of Integrinalpha2beta1 and CD133 in benign prostatic hyperplasia (BPH) complicated by prostatitis and their significance.

METHODSSpecimens were obtained from 56 BPH patients undergoing transvesical prostatectomy. Paraffin sections of the specimens were subjected to HE staining for pathological examination of inflammatory changes under the light microscope. Twenty-four patients with simple BPH were included in Group A, and the other 32 with BPH complicated with prostatitis in Group B. The expressions of Integrinalpha2beta1 and CD133 in the prostatic tissues of the two groups were determined by immunohistochemistry, Western blotting and IPP6.0 image analysis software.

RESULTSThe expressions of Integrinalpha2beta1 and CD133 were significantly higher in Group B than in A (P < 0.05), and so were the mean relative value of the optical density of Integrinalpha2beta1 (0.29 +/- 0.18 vs 0.04 +/- 0.03) and that of CD133 (0.08 +/- 0.07 vs 0.0020 +/- 0.0018) (P < 0.05).

CONCLUSIONInflammation can up-regulate the expressions of Integrinalpha2beta1 and CD133 in BPH tissue.

AC133 Antigen ; Antigens, CD ; metabolism ; Glycoproteins ; metabolism ; Humans ; Inflammation ; metabolism ; Integrin alpha2beta1 ; metabolism ; Male ; Peptides ; metabolism ; Prostatic Hyperplasia ; complications ; metabolism ; pathology ; Prostatitis ; complications ; metabolism ; pathology

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Humans ; Paxillin/metabolism* ; Protein-Lysine 6-Oxidase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Epithelial-Mesenchymal Transition ; Integrin alpha2beta1/metabolism* ; Mouth Neoplasms/pathology* ; Collagen/metabolism* ; Fibroblasts ; Extracellular Vesicles/metabolism* ; Cell Line, Tumor ; Tumor Microenvironment