BACKGROUND: Platelet-rich plasma (PRP) stimulates cell proliferation and enhances matrix gene expression and synthesis. However, there have been no comparative study of the PRP effect on the normal and degenerative tenocytes. The purpose of this study was to compare the effect of PRP on tenocytes from normal and degenerative tendon. METHODS: Tendon tissues were obtained from patients undergoing arthroscopic repair (n=9) and from healthy donors (n=3). Tenocytes were cultured with 10% (vol/vol) platelet-poor plasma, PRP activated with calcium, and PRP activated with calcium and thrombin. The total cell number was assessed at days 7 and 14. The expressions of type I and III collagen, decorin, tenascin-C, and scleraxis were evaluated by quantitative real-time reverse transcriptase polymerase chain reaction. The total collagen and glycosaminoglycan (GAG) synthesis was evaluated at days 7 and 14. RESULTS: No differences were observed between the groups at day 7, but cell proliferation was remarkably increased in tenocytes from the degenerative tendon at day 14. In both tenocyte groups, the gene expressions of type I and III collagen were up-regulated. GAG synthesis was greater in the normal tendon, whereas the expressions of decorin and tenascin-C were increased in tenocytes from the degenerative tendon. Tenocytes from the degenerative tendon had higher fold-change of GAG synthesis and a lower collagen III/I ratio than normal tenocytes. CONCLUSIONS: PRP promoted the cell proliferation and enhanced the synthesis of tendon matrix in both groups. PRP has a greater positive effect on cell proliferation, matrix gene expression and synthesis in tenocytes from degenerative tendon.
Calcium ; Cell Count ; Cell Proliferation ; Collagen ; Decorin ; Gene Expression ; Humans ; Plasma ; Platelet-Rich Plasma ; Reverse Transcriptase Polymerase Chain Reaction ; Rotator Cuff ; Tears ; Tenascin ; Tendons ; Thrombin ; Tissue Donors

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating infl ammation and fi brosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 (10 µmol/L) treatment as experimental models. Addition of NecroX-5 signifi cantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 (TGFβ1) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, signifi cantly increased production of tumor necrosis factor alpha (TNFα), TGFβ1, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of TNFα, TGFβ1, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway.
Animals ; Decorin ; Fibrosis ; Heart* ; Inflammation ; Liver ; Models, Theoretical ; Phosphorylation ; Rats* ; Reperfusion ; Reperfusion Injury ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

Formation of dermal collagen fiber is a complicated and sequential process with the progressive assembly of collagen. Collagen monomers form stepped and orderly protofibrils through longitudinal displacement. Subsequently, protofibrils or protofibrils and collagen are bonded by covalent bonds to form orderly lamellar structure of collagen fibers. Then collagen fibers are tightly wound into coarse collagen fiber bundles by covalent crosslinking. Decorin is a multifunctional small leucine-rich proteoglycan. It can prevent the aggregation of protofibrils by binding to the specific site of collagen with its core protein, and adjusting the spacing between the protofibrils with its glycosaminoglycan chain. Thus, by effecting the formation of collagen fibers with regulation of collagen assembly, decorin may help prevent scar formation and even promote regeneration.
Collagen ; Decorin ; metabolism ; Extracellular Matrix ; Extracellular Matrix Proteins ; metabolism ; pharmacology ; Fibrillar Collagens ; metabolism ; ultrastructure ; Fibrin ; metabolism ; Humans ; Microfibrils ; metabolism ; Proteoglycans ; metabolism ; pharmacology

BACKGROUNDLiver fibrosis normally progresses to cirrhosis and destroys the normal architecture of the liver, resulting in liver dysfunction and irreversible cirrhosis. The aim of this study was to investigate the anti-fibrosis effect and the possible underlying mechanisms of decorin.

METHODSThe mice model of liver fibrosis was induced by intraperitoneal injection of 50% (v/v) of carbon tetrachloride (CCl4) diluted in olive oil (1 ml/kg body weight) once every 2 days for 5 weeks. Three weeks after injecting CCl4 intraperitoneally, mice were randomly divided into normal control with vehicles only (olive oil), mouse model given CCl4 only, and CCl4 plus decorin (DCN, 250 µg/kg). Two weeks later, all the mice were sacrificed and their liver tissues were analyzed for the expressions of genes related to liver fibrosis and under hematoxylin-eosin staining, Masson staining, and immunohistochemical staining of all groups. Aspartate transaminase, alanine transaminase, and total bilirubin of the serum were determined for evaluation of the liver function.

RESULTSExogenous protein decorin could reduce liver fibrosis induced by CCl4 in mice. The degree of fibrosis in the experimental group was alleviated, and the contents of collagen fibers were lower in the experimental group than those of the control group. In addition, expressions of transforming growth factor β1 and α-smooth muscle actin decreased in the experimental group.

CONCLUSIONSTaking liver fibrosis model of mouse as the experimental target and by injecting exogenous protein decorin into the model, we confirmed that decorin could inhibit the expression of proteins related to fibrosis and reduce the formation of liver fibrosis in mice.

Animals ; Carbon Tetrachloride ; toxicity ; Decorin ; therapeutic use ; Immunohistochemistry ; Liver Cirrhosis ; chemically induced ; prevention & control ; Mice ; Transforming Growth Factor beta1 ; metabolism

BACKGROUNDConsidering the existence of a large number of liver cell degeneration and necrosis in fibrotic liver, liver function was damaged severely and could not effectively regenerate after partial hepatectomy (PHx). The aim of this study was to investigate whether decorin (DCN) could promote the liver regeneration after PHx in fibrotic mice.

METHODSForty mice (5-week-old, Balb/c) were injected with CCl4 intraperitoneally and liver fibrosis model was established after 5 weeks. The survival mice were randomly divided into two groups: control group and DCN group. Then, we performed 70% PHx on all these mice and injected DCN or phosphate-buffered saline plus normal saline (NS) to each group, respectively, after surgery. Liver body weight ratio (LBR), quantitative real-time polymerase chain reaction, and immunohistochemistry were used to analyze liver regeneration and fibrosis degree in both groups, and to find out whether exogenous protein DCN could promote the regeneration of fibrosis liver after PHx.

RESULTSExpressions of a-smooth muscle actin (SMA) mRNA and LBR had significant increases in the DCN group at postoperative Day 3 (POD 3, P < 0.05). The protein expressions of CD31, a-SMA, and tumor necrosis factor (TNF)-a were higher in the DCN group than those in the control group by immunohistochemistry at POD 3 (P < 0.05).

CONCLUSIONExogenous protein DCN could promote liver regeneration after PHx in fibrotic mice.

Animals ; Decorin ; therapeutic use ; Hepatectomy ; Immunohistochemistry ; Liver Cirrhosis ; drug therapy ; metabolism ; surgery ; Liver Regeneration ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism

Decorin is a member of the extracellular matrix small leucine-rich proteoglycans family that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that decorin affects the biology of various types of cancer by directly or indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis. More recent studies show that decorin plays important roles during tumor development and progression and is a potential cancer therapeutic agent. In this article, we summarize recent studies of decorin in cancer and discuss decorin's therapeutic and prognostic value.
Biomarkers, Tumor ; metabolism ; Cell Proliferation ; Decorin ; metabolism ; Extracellular Matrix ; metabolism ; Humans ; Neoplasm Metastasis ; Neoplasms ; metabolism ; pathology ; Neovascularization, Pathologic ; Prognosis

PURPOSE: To report the expression of decorin and TGF-beta in partial myotomy of the extraocular muscle in rats. METHODS: Partial myotomy of the superior rectus muscle was performed on the right eye of 10 Sprague-Dawley rats followed by exposure of the left superior rectus muscle and a simple suture of the conjunctiva. The bilateral superior rectus muscle was obtained from all rats at 2 weeks postoperatively. The tissues were observed under light microscopy with hematoxylin-eosin, Masson's trichrome staining and immunohistochemistry. RESULTS: Histological examinations of the surgical area at 2 weeks after postoperatively showed irregularly concentrated fibrosis on light microscopy with hematoxylin-eosin and Masson's trichrome staining of the experimental eyes. Immnohistochemistry showed that expression of decorin was in the same location as TGF-beta in the experimental group. CONCLUSIONS: The expression of decorin was found in the healing process after partial myotomy of the extraocular muscle in rats. Immunohistochemistry showed that expression of decorin was in the same location as with TGF-beta.
Animals ; Conjunctiva ; Decorin* ; Fibrosis ; Immunohistochemistry ; Microscopy ; Rats* ; Rats, Sprague-Dawley ; Sutures ; Transforming Growth Factor beta*

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

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 mechanisms of decorin inhibiting epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor beta1 (TGF-beta1) in renal tubular epithelial cells.

METHODHK-2 cells in vitro were divided into 4 groups: (1) negative control group; (2) decorin group, added with decorin 100 ng/ml ; (3) TGF-beta1 group, added with TGF-beta1 10 ng/ml; (4) decorin and TGF-beta1 group, added with decorin 100 ng/ml and TGF-beta1 10 ng/ml. The protein level of phosphor-ERK, phosphor-PI3K, phosphor-Smad(3) and beta-catenin was detected by Western blotting method. The snail mRNA level was tested by real time-PCR, while the lymphoid enhancer factor-1 (LEF-1) mRNA level was measured by RT-PCR.

RESULTSThe snail (2.59 +/- 0.70:1.02 +/- 0.13) and LEF-1 mRNA (1.85 +/- 0.08:0.30 +/- 0.11) were significantly up-regulated, meanwhile the protein level of phosphor-ERK (1.11 +/- 0.09:0.47 +/- 0.07), phosphor-PI3K (14.79 +/- 1.02:2.48 +/- 0.06), phosphor-Smad(3) (0.95 +/- 0.02:0.08 +/- 0.01) and beta-catenin (1.46 +/- 0.20:0.49 +/- 0.05) were significantly increased in TGF-beta1 group compared to control group, while there were no statistically significant difference in all figures between control group and decorin group. The phosphor-ERK protein level (0.58 +/- 0.08) and the snail mRNA level (1.24 +/- 0.03) were significantly down-regulated in TGF-beta1 and decorin group compared to TGF-beta1 group, however there were no statistically significant differences in the level of phosphor-PI3K (15.84 +/- 1.64), phosphor-Smad(3) (0.90 +/- 0.04) and beta-catenin (1.42 +/- 0.09) between these two groups.

CONCLUSIONDecorin inhibited EMT induced by TGF-beta1 which may be through blocking the ERK signal transduction pathway.

Cell Dedifferentiation ; drug effects ; Cells, Cultured ; Decorin ; pharmacology ; Epithelial Cells ; cytology ; Fibronectins ; Humans ; Kidney Tubules ; cytology ; pathology ; Proteoglycans ; Transforming Growth Factor beta1 ; metabolism