Liver fibrosis is a pathological process of the excessive accumulation of extracellular matrix, especially collagen al (I) in liver. Ultimately, hepatic fibrosis leads to cirrhosis or hepatic failure. Liver fibrosis and early cirrhosis can be reversed, thus control of the development of liver fibrosis is very important for preventive treatment of cirrhosis and hepatic failure. This is a review of potential targets for anti-hepatic fibrosis based on plenty of publications, including TGF-β1 and integrin α(v) and so on, aimed at providing novel therapeutic targets in liver fibrosis.
Collagen ; metabolism ; Humans ; Integrin alphaV ; metabolism ; Liver ; pathology ; Liver Cirrhosis ; drug therapy ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVE: This study was to investigate the expression and significance of Integrins subunits in laryngeal squamous cell carcinoma (LSCC). METHOD: The expression of Integrins subunits was detected by cDNA microarray in 4 cases of primary LSCC tissues and corresponding adjacent normal tissues. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) were used to identify the different expression of Integrins subunits in 24 cases of primary LSCC tissues and corresponding adjacent normal tissues. RESULT: A cDNA microarray analysis revealed significant changes in the expression of Integrins subunits, with IntegrinalphaV, Integrinbeta8 being up-regulated and Integrinalpha8 being down-regulated. The result of RT-PCR was consistent with that of cDNA microarray. The mRNA levels of IntegrinalphaV and Integrinbeta8 were significantly higher in LSCC tissues than that in corresponding adjacent normal tissues (1.0131 +/- 0.4780 vs 0.7591 +/- 0.4678 for IntegrinalphaV, P<0.05, 1.7362 +/- 1.3849 vs 1.2267 +/- 0.9363 for Integrinbeta8, P<0.05). The mRNA levels of Integrinalpha8 were significantly lower in LSCC tissues than that in corresponding adjacent normal tissues (0.2646 +/- 0.2622 vs 0.5457 +/- 0.3827, P<0.05). CONCLUSION The expression of IntegrinalphaV, Integrinbeta8, Integrinalpha8 were significantly up-regulated or down-regulated in laryngeal squamous cell carcinoma, which may relate to tumorigenesis and development of laryngeal squamous cell carcinoma.
Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Humans ; Integrin alpha Chains ; genetics ; metabolism ; Integrin alphaV ; genetics ; metabolism ; Integrin beta Chains ; genetics ; metabolism ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neoplasm Staging

OBJECTIVETo observe the effects of Bushen Zhuyun Recipe (BZR) on protein expressions of estrogen receptor (ER), progesterone receptor (PR) and integrin alpha5 and beta3 in endometrium of rats at the implantation stage, for exploring the possible mechanism of the recipe in treating luteal phase defect (LPD) infertility.

METHODSFemale SD rats were randomly divided into 6 groups, the blank group, the model group, the WM group treated by Western medicine, and the three BZR groups treated by low-, middle- and high-dose BZR respectively. Rats were made to pregnancy and sacrificed at the implantation stage, their middle segment of uterus, about 1 cm in length was gotten for detecting the protein expressions by Western blot. Results The protein expressions of endometrial ER and PR were significantly higher, while those of integrin alpha5 and beta3 were significantly lower than those of the control group (P < 0.05). The protein expressions of endometrial ER and PR were significantly lower, but those of integrin alpha5 and integrin beta3 were higher in rats treated by middle- and high- dose BZR than those in model rats (P < 0.05).

CONCLUSIONBZR can raise the receptivity of rats' endometrium through down-regulating the expressions of ER, PR and increasing the protein expression of integrin alpha5 and beta3 in endometrium and thus to enhance the pregnant rate.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Embryo Implantation ; drug effects ; physiology ; Endometrium ; drug effects ; metabolism ; Female ; Integrin alphaV ; metabolism ; Integrin beta3 ; metabolism ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

BACKGROUNDThe initial osteoblastic adhesion to materials characterizes the first phase of cell-material interactions and influences all the events leading to the formation of new bone. In a previous work, we developed a novel amorphous calcium phosphate (ACP)/poly(L-lactic acid) (PLLA) material that demonstrated morphologic variations in its microstructure. The aim of this study was to investigate the initial interaction between this material and osteoblastic cells. Cellular attachment and the corresponding signal transduction pathways were investigated.

METHODSA porous ACP/PLLA composite and PLLA scaffold (as a control) were incubated in fetal bovine serum (FBS) containing phosphate-buffered saline (PBS), and the protein adsorption was determined. Osteoblastic MG63 cells were seeded on the materials and cultured for 1, 4, 8, or 24 hours. Cell attachment was evaluated using the MTS method. Cell morphology was examined using scanning electron microscopy (SEM). The expression levels of the genes encoding integrin subunits α1, α5, αv, β1, focal adhesion kinase (FAK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using real-time reverse transcription polymerase chain reaction (RT-PCR).

RESULTSThe ACP/PLLA material significantly increased the protein adsorption by 6.4-fold at 1 hour and 2.4-fold at 24 hours, compared with the pure PLLA scaffold. The attachment of osteoblastic cells to the ACP/PLLA was significantly higher than that on the PLLA scaffold. The SEM observation revealed a polygonal spread shape of cells on the ACP/ PLLA, with the filopodia adhered to the scaffold surface. In contrast, the cells on the PLLA scaffold exhibited a spherical or polygonal morphology. Additionally, real-time RT-PCR showed that the genes encoding the integrin subunits α1, αv, β1, and FAK were expressed at higher levels on the ACP/PLLA composite.

CONCLUSIONSThe ACP/PLLA composite promoted protein adsorption and osteoblastic adhesion. The enhanced cell adhesion may be mediated by the binding of integrin subunits α1, αv, and β1, and subsequently may be regulated through the FAK signal transduction pathways.

Biocompatible Materials ; chemistry ; Calcium Phosphates ; chemistry ; Cell Adhesion ; physiology ; Cells, Cultured ; Focal Adhesion Protein-Tyrosine Kinases ; metabolism ; Humans ; Integrin alpha1 ; metabolism ; Integrin alpha5 ; metabolism ; Integrin alphaV ; metabolism ; Integrin beta1 ; metabolism ; Integrins ; genetics ; metabolism ; Lactic Acid ; chemistry ; Osteoblasts ; cytology ; Porosity ; Tissue Engineering ; methods

In postmenopausal osteoporosis, estrogen deficiency leads to unbalance of bone metabolism, decreased bone formation and increased bone resorption, and the result is reduced bone mineral density (BMD) and bone stiffness. The processes of bone formation and resorption involves the expression of integrins in anchoragedependent cells, such as osteoblast and osteoclast. The osteoporosis-induced rats frequently demonstrated the loss of trabecular bone volume in the tibia, vertebra and mandible due to estrogen depletion. However, in maxilla, study has been rare because of its anatomical limits. So the objective of this study was to investigate bony change and property of integrin expression in maxilla of osteoporosis-induced rats. 12-week-old female Sprague-Dawley rats were bilaterally ovariectomized (OVX). At 1, 2, 3, 4, 8 and 12 weeks, control and OVX group rats were sacrificed respectively. BMD of maxilla of the rats was measured using dual-energy X-ray absorptiometry (DEXA). And then the histopathologic observation, histomorphometric analysis and immunohistochemistry with CD44, alpha2 integrin, alpha5 integrin, alpha6 integrin, alphav integrin and beta3 integrin were done. BMD of alveolar bone in maxilla was decreased with significance statistically after OVX 4 weeks and was decreased 18.15% at OVX 12 weeks group compared to control group. From OVX 4 to 12 weeks, the thickness of periodontal ligament space was decreased, the number of osteoclast and the size of marrow stroma were increased than control group. By histomorphometric analysis, the size of marrow stroma of alveolar bone in maxilla was increased 86.42% at OVX 12 weeks group compared to control group. CD44 was widely expressed throughout the odontoblast, cementoblast, dental pulp, preiodontal ligament, osteocyte, osteoclast and perivascular tissue at control group, and CD44 immunoreactivity was increased the odontoblast, osteoblast and osteoclast at OVX groups. alpha2 integrin was expressed the odontoblast and osteoblast at control group, but alpha2 integrin immunoreactivity was decreased the osteoblast at OVX 12 weeks group. alpha5 integrin was expressed the cementoblast, osteoblast and osteoclast at control group, and alpha5 integrin immunoreactivity was decreased the osteoblast and was increased the osteoclast from OVX 4 weeks group. alpha6 integrin was weakly expressed the odontoblast, cementoblast, osteoblast and osteoclast at control group, and alpha6 integrin immunoreactivity was weakly increased the osteoclast from OVX 4 weeks. alphav integrin was expressed the odontoblast and osteoclast at control group, and alphav integrin immunoreactivity was strongly increased the osteoclast from OVX 4 weeks. beta3 integrin was expressed the osteocyte and osteoclast at control group, and beta3 integrin immunoreactivity was strongly increased the osteoclast from OVX 4 weeks. From these results, alveolar bone in maxilla of OVX rats was decreased BMD gradually. Moreover, alpha2 and alpha5 integrin expression of osteoblast was decreased, and alpha5, alphav and beta3 integrin expression of osteoclast was increased in OVX rats. Thus, this study indicates that consideration of reduced BMD is necessary in dental procedure of postmenopausal women.
Absorptiometry, Photon ; Animals ; Bone Density* ; Bone Marrow ; Bone Resorption ; Dental Cementum ; Dental Pulp ; Estrogens ; Female ; Humans ; Immunohistochemistry ; Integrin alpha2 ; Integrin alpha5 ; Integrin alpha6 ; Integrin alphaV ; Integrin beta3 ; Integrins ; Ligaments ; Mandible ; Maxilla* ; Metabolism ; Odontoblasts ; Osteoblasts ; Osteoclasts ; Osteocytes ; Osteogenesis ; Osteoporosis, Postmenopausal ; Ovariectomy* ; Periodontal Ligament ; Rats* ; Rats, Sprague-Dawley ; Spine ; Tibia

Binding of viruses to cell surface molecules is an essential step in viral infection. In vitro studies suggested that the alpha v beta3 integrin receptor is the epithelial cell receptor for Hantaan virus (HTNV). Whether beta3 is in vivo the only or central cellular receptor for HTNV infection is not known. To investigate the role of beta3 integrin for cellular entry of HTNV, we established an HTNV infection model in newborn murine pups. Infected pups died at an average age of 14.2 +/- 1.1 days with high levels of viral antigen detected in their brain, lung, and kidney. Pre-injection of blocking monoclonal antibodies (mAb) specific for either beta3 or av prolonged survival significantly to a maximal average survival of 19.7 +/- 1.5 days (P<0.01) and 18.4 +/- 0.9 days (P<0.01), respectively. XT-199, a chemical blocker of the alpha v beta3 receptor also prolonged survival to 19.5 +/- 1.3 days (P<0.01). In contrast to these receptor blockades, anti-HTNV antibody was not only able to prolong survival, but 20% of infected pups achieved long-term survival. An anti-murine beta1 antibody comparatively prolonged survival (19.0 +/- 1.2 days), suggesting that HTNV infection is partly mediated through integrin beta1 receptors as well as through beta3 receptors in vivo. Our data demonstrate that the beta3 receptor is important for HTNV infection in vivo, but also suggest that HTNV may utilize additional receptors beyond beta3 for cellular entry within an organism.
Animals ; Animals, Newborn ; Antibodies, Monoclonal/therapeutic use ; Antigens, CD29/metabolism ; Hantaan virus/*metabolism/pathogenicity ; Hemorrhagic Fever with Renal Syndrome/mortality/*virology ; Imidazoles/pharmacology ; Integrin alphaV/metabolism ; Integrin alphaVbeta3/antagonists & inhibitors ; Integrin beta3/*metabolism ; Mice ; Receptors, Virus/*metabolism ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.

Receptors play a crucial role in determining the pathogenesis and tissue tropism of virus. Foot-and-mouth disease virus (FMDV) has been showed to use four integrins, alphavbeta1, alphavbeta3, alphavbeta6 and alphavbeta8 as receptors to initiate infection. In this study, the porcine integrin alphav gene was cloned by RT-PCR from the lung tissue of healed pig infected experimently with FMDV, and compared its nucleotide and deduced amino acid sequence with the av gene of other animals. The 3141bp cDNA of bovine integrin alphav encodes a polypeptide of 1046 amino acids consisting of a 30-residue putative signal peptide, a 955-residue ectodomain, a 29-residue transmembrane domain, and a 32-residue cytoplasmic domain. The ectodomain contains 11 potential N-linked glycosylation sites (NXT/NXS), 2 calcium binding domains (DX[D/N] XDGXXD) and 18 cysteine residues. The nucleotide sequence similarities of integrin alphav between pig and cattle, human, rheses monkey, house mouse, chicken, dog are 93.3%, 91.5%, 91.4%, 85.6%, 73.2% and 89.9% respectively; and the amino acid sequence similarities are 96.3%, 94.6%, 94.1%, 90.8%, 81.6% and 93.8%, respectively. The alphav gene of cattle and pig exhibited the highest sequence homology. It is possible that host tropism of FMDV may related to divergence in receptors among different species.
Amino Acid Sequence ; Animals ; Base Sequence ; Cattle ; Cloning, Molecular ; DNA, Complementary ; genetics ; Foot-and-Mouth Disease Virus ; physiology ; Integrin alphaV ; genetics ; Macaca mulatta ; Molecular Sequence Data ; Receptors, Virus ; genetics ; metabolism ; Sequence Analysis ; Swine ; genetics

OBJECTIVETo test whether tanshinone II A (Tan II A), a highly valued herb derivative to treat vascular diseases in Chinese medicine, could protect endothelial cells from bacterial endotoxin (lipopolysaccharides, LPS)-induced endothelial injury.

METHODSEndothelial cell injury was induced by treating human umbilical vein endothelial cells (HUVECs) with 0.2 μg/mL LPS for 24 h. Y27632 and valsartan were used as positive controls. The effects of tanshinone II A on the LPS-induced cell viability and apoptosis rate of HUVECs were tested by flow cytometry, cell migration by transwell, adhesion by a 96-well plate pre-coated with vitronectin and cytoskeleton reorganization by immunofluorescence assay. Rho/Rho kinase (ROCK) pathway-associated gene and protein expression were examined by microarray assay; quantitative real-time polymerase chain reaction and Western blotting were used to confirm the changes observed by microarray.

RESULTSTan II A improved cell viability, suppressed apoptosis and protected cells from LPS-induced reductions in cell migration and adhesion at a comparable magnitude to that of Y27632 and valsartan. Tan II A, Y27632 and valsartan also normalized LPS-induced actomyosin contraction and vinculin protein aggregation. A microarray assay revealed increased levels of fibronectin, integrin A5 (ITG A5), Ras homolog gene family member A (RhoA), myosin light chain phosphatase, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K, or PIP2 in Western blotting), focal adhesion kinase, vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in the damaged HUVECs, which were attenuated to different degrees by Tan II A, Y27632 and valsartan.

CONCLUSIONTan II A exerted a strong protective effect on HUVECs, and the mechanism was caused, at least in part, by a blockade in the Rho/ROCK pathway, presumably through the down-regulation of ITG A5.

Apoptosis ; drug effects ; Cell Adhesion ; drug effects ; Cell Movement ; drug effects ; Cell Shape ; drug effects ; Cell Survival ; drug effects ; Cytoprotection ; drug effects ; Cytoskeleton ; drug effects ; metabolism ; Diterpenes, Abietane ; chemistry ; pharmacology ; Down-Regulation ; drug effects ; genetics ; Human Umbilical Vein Endothelial Cells ; drug effects ; enzymology ; pathology ; Humans ; Integrin alphaV ; metabolism ; Lipopolysaccharides ; Myosin Light Chains ; metabolism ; Oligonucleotide Array Sequence Analysis ; Phosphatidylinositol 4,5-Diphosphate ; metabolism ; Protective Agents ; pharmacology ; Signal Transduction ; drug effects ; Up-Regulation ; drug effects ; genetics ; Vinculin ; metabolism ; rho GTP-Binding Proteins ; metabolism ; rho-Associated Kinases ; metabolism