A 43-year-old man developed decreased vision in the right eye that had persisted for seven years. Under slit lamp examination, corneal clouding was noted with normal endothelium and ocular structure. From the clinical evidence, we suspected that the patient had congenital hereditary stromal dystrophy (CHSD). He and his family underwent a genetic analysis. Penetrating keratoplasty was conducted, and the corneal button was investigated for histopathologic confirmation via both light and electron microscopy. The histopathologic results revealed mildly loosened stromal structures, which exhibited an almost normal arrangement and differed slightly from the previous findings of CHSD cases. With regard to the genetic aspects, the patient and his mother harbored a novel point mutation of the decorin gene. This genetic mutation is also distinct from previously described deletion mutations of the decorin gene. This case involved delayed penetration of mild clinical symptoms with the histological feature of a loosened fiber arrangement in the corneal stroma. We concluded that this condition was a mild form of CHSD. However, from another perspective, this case could be considered as "decorin gene-associated corneal dystrophy," which is distinct from CHSD. Further evaluation will be required for appropriate clinical, histopathologic and genetic approaches for such cases.
Adult ; Corneal Dystrophies, Hereditary/diagnosis/*genetics ; Decorin/*genetics ; Humans ; Male ; Microscopy, Electron ; Pedigree ; *Point Mutation ; Republic of Korea

OBJECTIVETo investigate the content of decorin and its mRNA expression in normal human skin and hyperplastic scars at different stages, so as to explore the relationship between the change of decorin and its synthesis.

METHODSScar tissue samples from 22 patients undergoing scar excision and 10 specimens of normal skin or prepuce were obtained. The content and distribution of decorin in the tissue samples were determined with immunohistochemistry and Western blot, and the expression of decorin mRNA was detected by in situ hybridization.

RESULTSThe content of decorin was rich in the normal skin dermis with lower expression of the mRNA. In contrast, the decorin content was scarce in hyperplastic scars (HS) within 6 months, but increased gradually beginning from 7 to 12 months, and increased continuously for 13 to 36 months. There was no difference between the decorin content in normal skin and that in HS after 36 months (P > 0.05). Furthermore, the mRNA expression level in HS tissue was lower than that in normal skin within 6 months, but increased from 7 to 12 months. The mRNA expression continuously increased during 13 to 36 months and then returned to the level similar to that in normal skin thereafter.

CONCLUSIONThe decrease of decorin in hyperplastic scar was resulted primarily from reduced synthesis. The increase in decorin level coincided with the time of scar tissue stabilization, which implied that the delayed appearance was correlated with the formation of HS.

Blotting, Western ; Cicatrix, Hypertrophic ; metabolism ; Decorin ; Extracellular Matrix Proteins ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Proteoglycans ; analysis ; genetics ; RNA, Messenger ; analysis ; Skin ; chemistry

BACKGROUNDDecorin is a small leucine-rich proteoglycan and it plays an important role in regulation of cell growth and migration in various tumor cell lines. Decorin was found down-regulated in non-small cell lung cancer tissue and may be involved in regulation of lung cancer development.

METHODSIn this study, lentivirus-mediated RNA interference and over expression were employed to change the expression levels of decorin in lung cancer A549 cells. We tested the cell cycle of A549 cells and the expression of transforming growth factor (TGF)-β, cyclin D1, epidermal growth factor receptor (EGFR), P53, and P21.

RESULTSWe found that up-regulation of decorin could inhibit proliferation, block cell cycle at G1 and decrease invasive activity of A549 cells. Moreover, we also show that up-regulation of decorin induced significant decreases of TGF-β1, cyclin D1 expression, phosphorylation of EGFR, and increases of P53 and P21 expression. Opposite results were observed in A549 cells with down-regulation of decorin.

CONCLUSIONOur results suggest that decorin is a key regulator involved in proliferation and migration of A549 cells.

Cell Cycle ; genetics ; physiology ; Cell Movement ; genetics ; physiology ; Cell Proliferation ; Cyclin D1 ; genetics ; metabolism ; Decorin ; genetics ; metabolism ; Humans ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Transforming Growth Factor beta ; genetics ; metabolism ; Tumor Cells, Cultured

To screen differentially expressed genes involved in osteogenic differentiation of human bone marrow stromal cells (BMSCs) at defined stages, subtractive cDNA library was established by means of suppression subtractive hybridization. The BMSCs cultured for 12 and 21 d were used as driver and tester, respectively. A subtract library was successfully constructed and five positive clones were selected from the library. Sequencing analysis and homology comparison showed that the five clones differentially expressed in BMSCs cultured for 21 d were at least 90% homologous with the known genes in human GenBank. It was interestingly found that the osteogenic BMSCs cultured for 21 d differentially expressed decorin and Bax inhibitor 1. RT-PCR was performed to confirm the differentially expressed genes. The results showed that the expression of Bax inhibitor 1 was significantly higher in the cells of 21-day than that of 12-day, while the expression of decorin was only detected in the cells of 21-day.
Apoptosis Regulatory Proteins ; genetics ; metabolism ; Cell Differentiation ; genetics ; Cells, Cultured ; Decorin ; genetics ; metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Library ; Humans ; Membrane Proteins ; genetics ; metabolism ; Mesenchymal Stromal Cells ; cytology ; Osteoblasts ; cytology

OBJECTIVETo screen genes with abnormal expression in poorly-differentiated human lung adenocarcinoma at stage I with cDNA chip.

METHODSThe mRNA was extracted from cancer tissue and matched normal lung tissue, and was labeled by Cy5-dUTP or Cy3-dUTP as probes. Subsequently, the mixed probes were hybridized to the cDNA chip containing 8192 genes. The information was obtained by managing the cDNA chip with ScanArray4000 scanner and GenePix3.0 software.

RESULTSFive hundred and eighty genes were differentially expressed between cancer and normal lung tissue. Compared with normal lung tissue, 405 genes were up-regulated and 175 genes were down-regulated in cancer tissue. These genes are involved in different cell activities such as growth regulation and signal transduction. Among the 66 genes with remarkable differential expression between the two tissues, 39 were up-regulated and 27 down-regulated.

CONCLUSIONMany different kinds of genes are possibly involved in the initiation and progression of human lung adenocarcinoma. cDNA chip technique might be a useful method in screening lung cancer implicated genes.

Adenocarcinoma ; genetics ; pathology ; Cell Cycle ; Decorin ; Extracellular Matrix Proteins ; Female ; Gene Expression Profiling ; Humans ; Lung Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; methods ; Proteoglycans ; genetics

OBJECTIVESTo inject decorin-transfected mesangial cells (MsC) vector into the kidneys of rats with anti-thy-1 serum-induced nephritis via left renal artery and observe the survival condition of MsC vector and its influence on glomerular lesions in rats with anti-thy-1 serum induced nephritis.

METHODSRat mesangio-proliferative glomerulonephritis was established by tail intravenous injection with rabbit anti-thy-1 serum (ATS). Decorin-transfected MsC was injected into rat kidneys via left renal artery. Primary culture, immunostaining for BrdU and decorin of transfected MsC lines were performed to observe their survival. Immunohistochemistry with image analysis was performed to detect the expression of BrdU, alpha-SMA, decorin, TGF-beta1, FN and ColIV in diseased glomeruli.

RESULTSRat anti-thy-1 serum-induced nephritis identified by pathological examination was successfully established by injecting rabbit ATS, and decorin transfected MsC vector was transfused to rat glomeruli via left renal artery. The active growth and positive expressions of BrdU and decorin proteins on the nuclei and cytoplasms of ex vivo MsC were observed respectively. TGF-beta1, FN, ColIV expressions in diseased glomeruli of rats with ATS nephritis were decreased significantly at day 4 (TGF-beta1, P < 0.05) and day 2 (FN and ColIV, P < 0.01) respectively, compared to uninjected kidneys.

CONCLUSIONSMsC vector is successfully transferred to the glomeruli of experimental rats via left renal artery injection with no affect on cell survival. Decorin protein is expressed on the transfected MsC and shows antagonistic effect on the glomerular lesions of ATS rats. It suggests that the use of ex vivo MsC vector system can provide useful experimental basis for gene therapy of kidney disease in animal model.

Animals ; Decorin ; Disease Models, Animal ; Extracellular Matrix Proteins ; Genetic Therapy ; Glomerular Mesangium ; metabolism ; Glomerulonephritis, Membranoproliferative ; pathology ; therapy ; Immune Sera ; immunology ; Kidney Glomerulus ; pathology ; Proteoglycans ; genetics ; Rats ; Thy-1 Antigens ; immunology ; Transfection