beta ig-h3-Mediated Adhesion of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: beta ig-h3 is an extracellular matrix protein, which is overexpressed in synovial tissues of rheumatoid arthritis (RA) similar to adhesive glycoproteins. We sought to evaluate the compensatory role of beta ig-h3 with adhesive glycoproteins in mediating the adhesion of fibroblast- like synoviocytes (FLS) and to confirm the inhibitory effect of YH18 peptide of the 2nd fas-1 domain in beta ig-h3-mediated adhesion. METHODS: The adhesion of FLS isolated from synovial tissues of RA, was evaluated in 96 well microtiter plate coated with matrix proteins. Inhibitory effect of YH18 peptides from the 2nd and 4th fas-1 domains was estimated in beta ig-h3-mediated adhesion of FLS. RESULTS: The adhesion of FLS on beta ig-h3 was weaker than that of fibronectin and vitronectin. The beta ig-h3-mediated adhesion was enhanced by the stimulation with phorbol myristate acetate (PMA), but not by cytokines and growth factors. Combination of fibronectin with beta ig-h3 synergistically enhanced the adhesion of FLS, in contrast to the additive effect of vitronectin combined with beta ig-h3. YH18 peptide of the 2nd fas-1 domain did not block the beta ig-h3-mediated adhesion of FLS. CONCLUSION: Our results reveal that beta ig-h3 may regulate the adhesion of FLS through the interaction with adhesive glycoproteins and confirm that the essential motifs mediating adhesion on beta ig-h3 are different according to the type of cells.

The Relationship between the Histological Findings and beta ig-h3 in IgA Nephropathy / 대한신장학회잡지

BACKGROUND: TGF-beta is involved in the pathogenesis of various kidney diseases characterized by glomerulosclerosis and tubulointerstitial fibrosis. It is reported that urinary TGF-beta reflects the grade of interstitial fibrosis in glomerular disease. Here, we evaluated the relationship between the histological findings and beta ig-h3 in IgA nephropathy. METHODS: In patients with IgA nephropathy, we measured blood pressure (BP), serum creatinine, 24-hour urinary protein excretion (UTp), creatinine clearance (Ccr), serum and urine beta ig-h3 levels, and urine TGF-beta levels at the time of renal biopsy. Histologic findings were semiquantitively scored according to the extent of glomerulosclerosis (GG), tubulointerstitial fibrosis (TIG) and hyaline arteriolosclerosis (HA) by the criteria suggested by To. Semiquantitive scoring of immunohistochemistry for beta ig-h3 was done. RESULTS: Mean BP 95.4+/-14.5 mmHg, serum creatinine 1.06+/-0.35 mg/dL, 24-hour UTp 1, 423+/-1, 439 mg/day, and Ccr was 97.84+/-59.73 mL/min. The number of patients that showed GG 3 were 5, GG 2 was 1, GG 1 were 12. And, the number of patients that showed TIG 3 were 2, TIG 2 were 5, TIG 1 were 11. HA was shown in 4 patients. beta ig-h3 immunostaining was observed in glomerular Bowman's capsules and basement membrane of proximal tubules. The degree of beta ig-h3 immunostaining was positively correlated with the degree of glomerulosclerosis (r=0.72, p<0.001), interstitial fibrosis (r=0.91, p<0.001), serum creatinine (r=0.592, p<0.05) and Ccr (r=-0.626, p<0.05), but not with 24-hour UTp. Serum and urine beta ig-h3 levels did not correlate with any of these parameters. CONCLUSION: Renal beta ig-h3 expression in patients with IgA nephropathy may be related to glomerulosclerosis and interstitial fibrosis. However, urinary beta ig-h3 levels did not represent the pathologic changes of IgA nephropathy. Long-term study to measure renal beta ig-h3 expression and urinary beta ig-h3 is required to elucidate the roles of beta ig-h3 in IgA nephropathy.

Renal Expression and Usefulness of TGF-beta-inducible Gene-h3 in Human Type II Diabetic Nephropathy -Immunohistochemical Analysis- / 대한신장학회잡지

BACKGROUND: Activation of transforming growth factor-beta (TGF-beta) system has been implicated in the pathological change of diabetic nephropathy such as renal hypertrophy and accumulation of extracellular matrix. In tissues, TGF-beta is secreted as a biologically inactive complex requiring in vivo activation. Thus, increased TGF-beta1 mRNA or protein may not necessarily reflect parallel changes in TGF-beta1 biologic activity. TGF-beta1 inducible gene-h3 (betaig-h3) is a novel gene uniquely up-regulated by active TGF-beta1. METHODS: For evaluating the beta ig-h3 protein expression in human diabetic nephropathy, we examed the expression of beta ig-h3 protein, TGF-beta1, TGF-beta type II receptor (TRII) and Smad protein intranuclear translocation by immunohistochemistry in human diabetic nephropathy tissues (n=11) and normal renal tissue (n=3). RESULTS: The beta ig-h3 protein was expressed in diabetic tubular epithelium (diabetes vs. normal 7/11 vs. 0/3) and diabetic glomerulus (diabetes vs. normal 5/11 vs. 0/3). The tubular expression was stronger than the interstitial expression. The TGF-beta1 was expressed in diabetic tubular epithelium (diabetes vs. normal 1/11 vs. 0/3) and diabetic glomerulus (diabetes vs. normal 3/11 vs. 0/3). The TGF-beta type II was expressed more in diabetic glomerulus (diabetes vs normal 6/11 vs. 1/3). But in the tubule, the expression didn't show any significant difference. The number of intranuclear translocation of Smad protein in glomerulus (diabetes vs normal 49.1+/-0.3 vs. 40.1+/-0.8) was increased in diabetes, but the tubular manifestation was not significant. CONCLUSION: We propose that TGF-beta system mediates human diabetic nephropathy through beta ig- h3 protein expression. The beta ig-h3 protein expression could be a useful marker expecting of disease activity and progress.

Effect of beta-Ig H3 on Chondrogenesis by Human Bone Marrow Mesenchymal Stem Cells / 대한정형외과학회잡지

PURPOSE: This study was undertaken to compare the activity of beta-Ig H3 (BigH3) and transforming growth factor (TGF)-beta on chondrogenesis by mesenchymal stem cells (MSCs). MATERIALS AND METHODS: MSCs in human bone marrow aspirated from 20 healthy donors were isolated by density gradient Ficoll-hypaque separation and expanded in culture. MSC-alginate beads were prepared and incubated for 28 days in the presence of 0.5 or 10 ng/mL of TGF-beta 1, TGF-beta 1+TGF-beta 3 or BigH3. Cellular viability, total collagen and glycosaminoglycan (GAG) contents were measured and compared. SPSS version 9.0 was used for the statistical analysis. RESULTS: TGF-beta 3 significantly enhanced cell viability in beads by day 21 (p=0.029). No significant differences were found in terms of cell viability (p=0.197) or in total GAG content (p=0.253) between 10 ng/mL of TGF-beta 1+3 and 10 ng/mL of BigH3. Total collagen content was higher in the BigH3 added group on day 21 (p=0.041). CONCLUSION: The replacement of BigH3 instead of TGF-beta produced appropriate external signals indicating the chondrogenic differentiation of human bone marrow MSCs.