• Albumin
• DNA-binding protein from starved cells
• Kidney-targeting peptide
• Low molecular weight protein
• Lysozyme
• The ferritin family

• Humans
• Kidney/metabolism
• Proteins/chemistry
• Peptides/chemistry
• Drug Delivery Systems
• Kidney Diseases/drug therapy

• 3D culture
• CD44
• Spp1
• integrin
• macrophage
• osteopontin
• prostate intraepithelial neoplasia
• prostate tumor growth

• Cytokines/pharmacology
• Humans
• Macrophages/pathology
• Male
• Osteopontin/genetics
• Prostate/pathology
• Prostatic Intraepithelial Neoplasia/pathology
• Prostatic Neoplasms/pathology
• Proto-Oncogene Proteins c-akt

• U54 MD007590 NIMHD NIH HHS
• U54MD007590 NIMHD NIH HHS
• R25G06414 NIGMS NIH HHS
• U54 MD013376 NIMHD NIH HHS
• G12 MD007590 NIMHD NIH HHS
• T34 GM145508 NIGMS NIH HHS
• SC1 GM140907 NIGMS NIH HHS

Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg¹⁶⁸ [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg¹⁶⁸ from OPN-R to OPN-Leu¹⁶⁷ (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases.

• adult T-cell leukemia
• dengue virus
• hepatitis C virus
• human immunodeficiency virus
• infectious disease
• leptospirosis
• matrix metalloproteinase
• osteopontin
• proteases
• tuberculosis

Background  Alcoholic liver disease (ALD) is a major source of alcohol-related morbidity and mortality. Heavy drinkers and alcoholics may progress from fatty liver to alcoholic hepatitis to cirrhosis. The enzyme γ-glutamyltranspeptidase (GGT) is a membrane-bound glycoprotein which catalyzes the transfer of the γ-glutamyl group from γ-glutamyl peptides to other peptides, amino acids, and water. Serum GGT activity mainly attributed to hepatobiliary system and thus is an important marker of ALD. Hence the present study is conducted to estimate and correlate the levels of GGT and osteopontin (OPN) in ALD.

Aims and Objectives  The objective of this study is to estimate and correlate the levels of GGT and OPN in ALD.

Materials and Methods  Sixty clinically diagnosed cases of ALD and sixty age- and gender-matched healthy controls were recruited for the study. Blood samples were collected from them and serum aspartate aminotransferase, serum alanine transaminases (ALTs), serum ALP levels, and plasma OPN levels were measured. Estimation of serum aspartate transaminases (AST), ALTs, and alkaline phosphatase (ALP) was assayed by standard photometric methods in autoanalyzer ERBA-XL (EM-200) using commercially available kits. OPN was estimated by using commercial kit based on enzyme-linked immunosorbent assay.

Results  The parameters of the liver function tests such as AST, ALT, and ALP were significantly increased in patients with ALD ( p  < 0.001) when compared with the healthy control subjects. In the present study, significantly increased levels of γ-glutamyl transferases and OPN were found in patients with ALD ( p  < 0.001) when compared with the control subjects. OPN showed significant positive correlations with AST ( r  = 0.76, p  < 0.001), ALT ( r  = 0.64, p  < 0.001), ALP ( r  = 0.68, p  < 0.001), and GGT ( r  = 0.61, p  < 0.001).

Conclusion  The present study focuses on the role of GGT and OPN that are sensitive indicators of liver cell injury and are most helpful in recognizing hepatocellular diseases such as ALD, hepatitis, and liver cirrhosis. Hence, the pattern of the GGT and OPN levels elevation can be helpful diagnostically.

The extracellular matrix provides an important scaffold for cells and tissues of multicellular organisms. The scaffold not only provides a secure anchorage point, but also functions as a reservoir for signalling molecules, sequestered and released when necessary. A dysregulated extracellular matrix may therefore modulate cellular behaviour, as seen during cancer progression. The extracellular matrix protein nephronectin was discovered two decades ago and found to regulate important embryonic developmental processes. Loss of either nephronectin or its receptor, integrin α8β1, leads to underdeveloped kidneys. Recent findings show that nephronectin is also dysregulated in breast cancer and plays a role in promoting metastasis. To enable therapeutic intervention, it is important to fully understand the role of nephronectin and its receptors in cancer progression. In this review, we summarise the literature on nephronectin, analyse the structure and domain-related functions of nephronectin and link these functions to potential roles in cancer progression.

The extracellular matrix protein nephronectin plays an important regulatory role during embryonic development, controlling renal organogenesis through integrin α8β1 association. Nephronectin has three main domains: five N-terminal epidermal growth factor-like domains, a linker region harbouring two integrin-binding motifs (RGD and LFEIFEIER), and a C-terminal MAM domain. In this review, we look into the domain-related functions of nephronectin, and tissue distribution and expression. During the last two decades it has become evident that nephronectin also plays a role during cancer progression and in particular metastasis. Nephronectin is overexpressed in both human and mouse breast cancer compared to normal breast tissue where the protein is absent. Cancer cells expressing elevated levels of nephronectin acquire increased ability to colonise distant organs. In particular, the enhancer-motif (LFEIFEIER) which is specific to the integrin α8β1 association induces viability via p38 MAPK and plays a role in colonization. Integrins have long been desired as therapeutic targets, where low efficiency and receptor redundancy have been major issues. Based on the summarised publications, the enhancer-motif of nephronectin could present a novel therapeutic target.

• breast cancer
• cancer
• cancer progression
• extracellular matrix
• metastasis
• nephronectin

• cell adhesion
• cleft lip/palate
• convergence and extrusion
• cytoskeleton dynamics
• epithelial seam
• epithelial-mesenchymal transition
• extracellular matrix
• neural crest cells
• periderm
• primary cilia

• Autosomal dominant polycystic kidney disease
• Basement membrane
• Cyst growth
• ECM
• Focal adhesion kinase
• Integrin-linked kinase

The extracellular matrix protein nephronectin (Npnt) is known to be critical for kidney development, but its function in inflammatory diseases is unknown. Here, we developed a new enzyme‐linked immunosorbent assay system to detect Npnt in various autoimmune diseases, which revealed that plasma Npnt levels are increased in various mouse autoimmune models. We also report that antibodies against the α8β1 integrin‐binding region of Npnt protect mice from anti‐type II collagen‐induced arthritis, suggesting that Npnt may be a potential therapeutic target molecule for the prevention of autoimmune arthritis.

• ELISA
• anti-type II collagen-induced arthritis
• antibody
• autoimmune diseases
• nephronectin

• chronic wounds
• non-healing ulcers
• osteopontin
• wound healing

• Animals
• Basic-Leucine Zipper Transcription Factors/genetics
• Cell Line, Tumor
• Dendritic Cells/immunology
• Female
• Fibrosarcoma/genetics
• Fibrosarcoma/immunology
• Graft Rejection/genetics
• Graft Rejection/immunology
• Interferon Regulatory Factors/genetics
• Lymph Nodes/immunology
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Oligonucleotide Array Sequence Analysis
• Repressor Proteins/genetics
• Spleen/immunology

• R01 AI150297 NIAID NIH HHS
• Howard Hughes Medical Institute

• Cell proliferation
• Collagen synthesis
• Integrin αvβ3
• Keloid
• Mechanical tension
• Mesenchymal stem cells

• axon regeneration
• integrin
• kindlin
• receptor activation state
• selective polarised transport
• traumatic injury of the nervous system

• Animals
• Axons/physiology
• Gene Expression Regulation/physiology
• Integrins/genetics
• Integrins/metabolism
• Nerve Regeneration/physiology
• Wounds and Injuries

• G1000864 Medical Research Council
• MR/R004463/1 Medical Research Council
• MR/R004544/1 Medical Research Council

• Bone toughness
• Collagen
• Mechanical testing
• Osteopontin
• Transglutaminase

• Animals
• Collagen/chemistry
• Collagen Type I/metabolism
• Durapatite/chemistry
• Fractures, Bone/metabolism
• GTP-Binding Proteins/metabolism
• Osteocalcin/metabolism
• Osteopontin/metabolism
• Polymers/chemistry
• Protein Glutamine gamma Glutamyltransferase 2
• Transglutaminases/metabolism

• ALCAM
• Itga8
• mesothelial cells
• myofibroblasts
• podoplanin
• septum transversum mesenchyme

• cell biology and structure
• cell-matrix-interactions
• glomerular basement membrane
• mesangial cells
• nephronectin

• Extracellular matrix
• Fibronectin
• Osteopontin
• Single chain variable fragment antibody (scFv)

• Differentially expressed genes
• Gene Ontology
• H. contortus
• Illumina HiSeq 4000 platform
• Kyoto Encyclopedia of Genes and Genomes

Tumour progression is dependent on the interaction between tumour cells and cells of the surrounding microenvironment. The tumour is a dynamic milieu consisting of various cell types such as endothelial cells, fibroblasts, cells of the immune system and mesenchymal stem cells (MSCs). MSCs are multipotent stromal cells that are known to reside in various areas such as the bone marrow, fat and dental pulp. MSCs have been found to migrate towards inflammatory sites and studies have shown that they also migrate towards and incorporate into the tumour. The key question is how they interact there. MSCs may interact with tumour cells through paracrine signalling. On the other hand, MSCs have the capacity to differentiate to various cell types such as osteocytes, chondrocytes and adipocytes and it is possible that MSCs differentiate at the site of the tumour. More recently it has been shown that cross-talk between tumour cells and MSCs has been shown to increase metastatic potential and promote epithelial-to-mesenchymal transition. This review will focus on the role of MSCs in tumour development at various stages of progression from growth of the primary tumour to the establishment of distant metastasis.

• Cancer progression
• Mesenchymal stem cells
• Tumour metastasis
• Tumour microenvironment
• Tumour stroma

• Itga8
• fibronectin
• human
• integrins
• osteopontin
• placenta
• placental pathologies
• rodent

Osteopontin (OPN), a multifunctional protein, is involved in numerous pathological conditions including inflammation, immunity, angiogenesis, fibrogenesis and carcinogenesis in various tissues. Extensive studies have elucidated the critical role of OPN in cell signaling such as regulation of cell proliferation, migration, inflammation, fibrosis and tumor progression. In the liver, OPN interacts with integrins, CD44, vimentin and MyD88 signaling, thereby induces infiltration, migration, invasion and metastasis of cells. OPN is highlighted as a chemoattractant for macrophages and neutrophils during injury in inflammatory liver diseases. OPN activates hepatic stellate cells (HSCs) to exert an enhancer in fibrogenesis. The role of OPN in hepatocellular carcinoma (HCC) has also generated significant interests, especially with regards to its role as a diagnostic and prognostic factor. Interestingly, OPN acts an opposing role in liver repair under different pathological conditions. This review summarizes the current understanding of OPN in liver diseases. Further understanding of the pathophysiological role of OPN in cellular interactions and molecular mechanisms associated with hepatic inflammation, fibrosis and cancer may contribute to the development of novel strategies for clinical diagnosis, monitoring and therapy of liver diseases.

• Osteopontin
• fibrosis
• hepatocellular carcinoma.
• inflammation
• liver injury

Osteopontin is a proinflammatory cytokine and plays a pathogenetic role in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), by recruiting autoreactive T cells into the central nervous system. Osteopontin functions are modulated by thrombin cleavage generating N- and C-terminal fragment, whose individual roles are only partly known. Published data are difficult to compare since they have been obtained with heterogeneous approaches. Interestingly, thrombin cleavage of osteopontin unmasks a cryptic domain of interaction with α₄β₁ integrin that is the main adhesion molecule involved in lymphocyte transmigration to the brain and is the target for natalizumab, the most potent drug preventing relapses. We produced recombinant osteopontin and its N- and C-terminal fragments in an eukaryotic system in order to allow their posttranslational modifications. We investigated, in vitro, their effect on human cells and in vivo in EAE. We found that the osteopontin cleavage plays a key role in the function of this cytokine and that the two fragments exert distinct effects both in vitro and in vivo. These findings suggest that drugs targeting each fragment may be used to fine-tune the pathological effects of osteopontin in several diseases.

Coordinated gastrointestinal smooth muscle contraction is critical for proper nutrient absorption and is altered in a number of medical disorders. In this work, we demonstrate a critical role for the RGD-binding integrin α8β1 in promoting nutrient absorption through regulation of gastrointestinal motility. Smooth muscle-specific deletion and antibody blockade of α8 in mice result in enhanced gastric antral smooth muscle contraction, more rapid gastric emptying, and more rapid transit of food through the small intestine leading to malabsorption of dietary fats and carbohydrates as well as protection from weight gain in a diet-induced model of obesity. Mechanistically, ligation of α8β1 by the milk protein Mfge8 reduces antral smooth muscle contractile force by preventing RhoA activation through a PTEN-dependent mechanism. Collectively, our results identify a role for α8β1 in regulating gastrointestinal motility and identify α8 as a potential target for disorders characterized by hypo- or hyper-motility.

DOI:http://dx.doi.org/10.7554/eLife.13063.001

Animals absorb nutrients from the food they eat in a complicated process that involves multiple steps. In the mouth, teeth break down the food into smaller chunks. Then the food passes through the stomach and small intestine, where enzymes break it down into individual molecules that are small enough to be absorbed by cells that line the small intestine. These cells then package the molecules and release them into the bloodstream so that they can be distributed to the rest of the body.

Muscles in the wall of the small intestine control how quickly food travels through this part of the gut. If food moves too quickly, the cells that line the intestine have less time to absorb the food molecules and may fail to absorb enough nutrients. If the food moves too slowly, an individual may experience nausea or vomiting, or the contents of their stomach may spill into their lungs.

In 2014, researchers reported that a protein in breast milk called Mfge8 helps to boost the number of fat molecules absorbed from food. Now, Khalifeh-Soltani et al. – including some of the same researchers involved in the earlier work – show that Mfge8 also slows the rate at which food travels through the small intestine in mice. Mfge8 binds to another protein called integrin α8β1 to control how often the intestine muscles contract. Genetically engineered mice that lacked integrin α8β1 developed diarrhea and food passed through their intestines more quickly than in normal mice. Furthermore, these mice did not gain as much weight as normal mice when they were fed a high-fat diet.

Khalifeh-Soltani et al.’s findings show that Mfge8 has a dual role in controlling the absorption of food molecules in the small intestine. The next challenge is to find out whether drugs that alter the activity of integrin α8β1 could be used to help treat patients with diseases in which food moves too quickly, or too slowly, through the gut.

DOI:http://dx.doi.org/10.7554/eLife.13063.002

• Mfge8
• PTEN
• cell biology
• gastrointestinal motility
• human
• integrin
• mouse
• nutrient absorption
• smooth muscle

Osteopontin (OPN), a secreted protein involved in inflammatory processes and cancer, induces cell adhesion, migration, and activation of inflammatory pathways in various cell types. Cells bind OPN via integrins at a canonical RGD region in the full length form as well as to a contiguous cryptic site that some have shown is unmasked upon thrombin or matrix metalloproteinase cleavage. Thus, the adhesive capacity of osteopontin is enhanced by proteolytic cleavage that may occur in inflammatory conditions such as obesity, atherosclerosis, rheumatoid arthritis, tumor growth and metastasis. Our aim was to inhibit cellular adhesion to recombinant truncated proteins that correspond to the N-terminal cleavage products of thrombin- or matrix metalloproteinase-cleaved OPN in vitro. We specifically targeted the cryptic integrin binding site with monoclonal antibodies and antisera induced by peptide immunization of mice. HEK 293 cells adhered markedly stronger to truncated OPN proteins than to full length OPN. Without affecting cell binding to the full length form, the raised monoclonal antibodies specifically impeded cellular adhesion to the OPN fragments. Moreover, we show that the peptides used for immunization were able to induce antisera, which impeded adhesion either to all OPN forms, including the full-length form, or selectively to the corresponding truncated recombinant proteins. In conclusion, we developed immunological tools to selectively target functional properties of protease-cleaved OPN forms, which could find applications in treatment and prevention of various inflammatory diseases and cancers.

• Animals
• Antibodies, Monoclonal, Murine-Derived/immunology
• Cell Adhesion/genetics
• Cell Adhesion/immunology
• Epitopes/genetics
• Epitopes/immunology
• Gelatinases/genetics
• Gelatinases/immunology
• HEK293 Cells
• Humans
• Mice
• Osteopontin/genetics
• Osteopontin/immunology
• Proteolysis
• Thrombin/genetics
• Thrombin/immunology

• TIMP-1
• VEGF
• fetal nephrotoxicity
• in utero exposure
• metals
• osteopontin

• Adhesion dependent apoptosis
• Epididymal anti sticking factor
• Soluble lectin

• Non-small cell lung cancer
• biomarker
• osteopontin
• prognosis

• BSA, bovine serum albumin
• FCS, fetal calf serum
• FN, fibronectin
• cell adhesion
• fibrillin-1
• glomerulonephritis
• glomerulus
• integrins
• mesangial cells
• migration
• sd, standard deviation
• wt, wild-type.
• α8 integrin-deficient mice
• α8−/−, alpha8 integrin-deficient

• ApoE-deficient mice
• atherosclerosis
• carotid artery ligation
• glomerulosclerosis
• integrins
• remodelling
• α8 integrin-deficient mice

• Implantation
• Integrins
• Pigs
• Psteoponti
• Sheep

• basement membrane
• cell adhesion
• extracellular matrix (ECM)
• integrin

• basement membrane
• cell adhesion
• extracellular matrix (ECM)
• integrin

• Animals
• Arthritis, Rheumatoid/metabolism
• Arthritis, Rheumatoid/pathology
• Cartilage, Articular/metabolism
• Cartilage, Articular/pathology
• Humans
• Osteopontin/metabolism
• Synovial Membrane/metabolism
• Synovial Membrane/pathology

• CCN
• Cell adhesion
• Extracellular matrix
• Fibulin
• Hevin
• Matricellular
• Osteopontin
• Periostin
• R-spondin
• Regenerative medicine
• SPARC
• Tenascins
• Thrombospondins

• Alternative Splicing/physiology
• Animals
• Biomarkers/metabolism
• CCN Intercellular Signaling Proteins/metabolism
• Extracellular Matrix Proteins/metabolism
• Extracellular Matrix Proteins/physiology
• Gene Expression Regulation/physiology
• Humans
• Mice
• Models, Biological
• Osteonectin/metabolism
• Protein Processing, Post-Translational/physiology
• Receptors, Antigen/metabolism
• Thrombospondin 1/metabolism
• Tissue Engineering/methods
• Translational Research, Biomedical/methods
• Translational Research, Biomedical/trends

• R13 DK100244 NIDDK NIH HHS
• R13DK100244 NIDDK NIH HHS

Systemic lupus erythematosus (SLE) is a multisystemic disease, caused by a variety of factors, which lead to immunological abnormalities. Osteopontin (OPN) is a pleiotropic protein, important in bone remodeling and immune system signaling. OPN, produced by various cells, including immune cells, plays a key role in regulating T-helper 1/T-helper 2 balance, stimulating B lymphocytes to produce antibodies, regulating macrophages, neutrophils and inducing dendritic cells. OPN expression is influenced by genetic polymorphisms of its promoter, hormones and cytokines. Over expression of OPN has been associated with the pathogenesis of immune-mediated diseases. OPN has been implicated in the development of murine model of lupus and in humans with SLE. In this review, I will present current state of research on the role of OPN and OPN gene polymorphisms in pathogenesis and clinical course of SLE. A better understanding of the role of OPN in SLE will contribute to more precise diagnosis and treatment of the disease.

• Actins/metabolism
• Animals
• Collagen Type I/metabolism
• Cytokines/metabolism
• Disease Models, Animal
• Epithelial Cells/metabolism
• Fibrillin-1
• Fibrillins
• Fibroblasts/metabolism
• Fibronectins/metabolism
• Fibrosis
• Integrin alpha Chains/metabolism
• Kidney Diseases/drug therapy
• Kidney Diseases/metabolism
• Kidney Diseases/pathology
• Kidney Tubules/metabolism
• Kidney Tubules/pathology
• Male
• Mice
• Mice, Knockout
• Microfilament Proteins/metabolism
• Molecular Targeted Therapy
• Osteopontin/metabolism
• Protein Transport
• Rats
• Rats, Sprague-Dawley
• Ureteral Obstruction/metabolism
• Ureteral Obstruction/pathology

• Animals
• Embryonic Development
• Female
• Fetal Development
• Humans
• Interferon Type I/metabolism
• Interferon Type I/physiology
• Maternal Nutritional Physiological Phenomena
• Osteopontin/metabolism
• Osteopontin/physiology
• Pregnancy
• Pregnancy Proteins/metabolism
• Pregnancy Proteins/physiology
• Signal Transduction
• TOR Serine-Threonine Kinases/metabolism
• TOR Serine-Threonine Kinases/physiology
• Uterus/growth & development
• Uterus/metabolism
• Uterus/physiology

• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Cell Cycle Checkpoints/genetics
• Cell Line
• Cell Proliferation
• Cell Transformation, Neoplastic/metabolism
• Cell Transformation, Neoplastic/pathology
• Cellular Senescence/genetics
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p21/genetics
• Cyclin-Dependent Kinase Inhibitor p21/metabolism
• Fibroblasts/cytology
• Fibroblasts/metabolism
• Humans
• Keratinocytes/cytology
• Keratosis/metabolism
• Mitogen-Activated Protein Kinase Kinases/metabolism
• Mutation
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Osteopontin/genetics
• Osteopontin/metabolism
• Precancerous Conditions/metabolism
• Precancerous Conditions/pathology
• Skin Neoplasms/metabolism
• Skin Neoplasms/pathology

• R01 CA130919 NCI NIH HHS
• 5 R01 CA130919 NCI NIH HHS

• Animals
• Basement Membrane/cytology
• Basement Membrane/metabolism
• Epidermal Cells
• Epidermis/metabolism
• Extracellular Matrix Proteins/metabolism
• Gene Expression Regulation
• Hair Follicle/cytology
• Integrin alpha Chains/metabolism
• Mice
• Myocytes, Smooth Muscle/cytology
• Myocytes, Smooth Muscle/metabolism
• Stem Cells/metabolism
• Wnt Proteins/metabolism
• beta Catenin/metabolism

• R01 NS019090 NINDS NIH HHS
• R01 NS019090-19 NINDS NIH HHS
• Cancer Research UK
• NS19090 NINDS NIH HHS

Extracellular matrix receptors of the integrin family are known to regulate cell adhesion, shape and functions. The α8 integrin chain is expressed in glomerular mesangial cells and in vascular smooth muscle cells. Mice deficient for α8 integrin have structural alterations in glomeruli but not in renal arteries. For this reason we hypothesized that mesangial cells and vascular smooth muscle cells differ in their respective capacity to compensate for the lack of α8 integrin.

Wild type and α8 integrin-deficient mesangial cells varied markedly in cell morphology and expression or localization of cytoskeletal molecules. In α8 integrin-deficient mesangial cells α-smooth muscle actin and CTGF were downregulated. In contrast, there were no comparable differences between α8 integrin-deficient and wild type vascular smooth muscle cells. Expression patterns of integrins were altered in α8 integrin-deficient mesangial cells compared to wild type mesangial cells, displaying a prominent overexpression of α2 and α6 integrins, while expression patterns of the these integrins were not different between wild type and α8 integrin-deficient vascular smooth muscle cells, respectively. Cell proliferation was augmented in α8 integrin-deficient mesangial cells, but not in vascular smooth muscle cells, compared to wild type cells.

Our findings suggest that α8 integrin deficiency has differential effects in mesangial cells and vascular smooth muscle cells. While the phenotype of vascular smooth muscle cells lacking α8 integrin is not altered, mesangial cells lacking α8 integrin differ considerably from wild type mesangial cells which might be a consequence of compensatory changes in the expression patterns of other integrins. This could result in glomerular changes in α8 integrin-deficient mice, while the vasculature is not affected in these mice.