Animals ; Extracellular Matrix ; metabolism ; Humans ; Kidney Glomerulus ; pathology ; Matrix Metalloproteinase 2 ; analysis ; physiology ; Sclerosis

Cell Adhesion Molecules ; metabolism ; Extracellular Matrix Proteins ; metabolism ; Humans ; Neoplasms ; metabolism ; pathology ; Thrombospondin 1 ; metabolism

The hallmark of scleroderma is fibrosis by excessive extracellular matrix (ECM) deposition in the skin, lung, and other organs. Increasing evidence suggests that overexpression of transforming growth factor-beta (TGF-beta) and its receptors play a key pathogenic role in the development of tissue fibrosis in scleroderma. TGF-beta is known to induce the expression of ECM proteins in the pathogenesis of fibrosis in systemic sclerosis. Investigations into TGF-beta pathways will suggest new treatment strategies for fibrotic diseases.
Animals ; Extracellular Matrix ; metabolism ; pathology ; Extracellular Matrix Proteins ; metabolism ; Fibroblasts ; metabolism ; Fibrosis ; Humans ; Receptors, Transforming Growth Factor beta ; metabolism ; Scleroderma, Systemic ; etiology ; metabolism ; Transforming Growth Factor beta ; metabolism

In acute injury, liver recovers completely without any scarring change or complication. However, large portion of liver is changed into fibrotic state by excessive production of extracellular matrix (ECM) under chronic injury. Excessive production of ECM results in hepatic fibrosis and repeated process of hepatic fibrosis progress into liver cirrhosis. Liver cirrhosis is an irreversible and terminal state of chronic liver disease and one of the major causes of death in Korea. To block the progression to liver cirrhosis, various studies in the field of virology and immunology have been proceeded. Recently, studies on the hepatic fibrogenesis have progressed with the development of molecular biology. Hepatic stellate cells (HSC) play a key role in the pathogenesis of hepatic fibrosis by producing ECM. The degree of hepatic fibrosis depends on the proliferation and activation of HSC and increased net production of collagen. Therefore, inhibition of HSC activation is one of the main ways to block the progression of hepatic fibrosis. Many kinds of factors such as oxidative stress, acetaldehyde, ascorbic acid, transforming growth factor-beta (TGF-beta) and carbon tetrachloride (CCl4) have been reported to activate HSC and stimulate collagen gene expression. Although there are no definite and effective antifibrogenic agents, possible candidates are antioxidants, interferon, retinoids such as beta-carotene, flavonoids, renin-angiotensin system inhibitors and peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonists. We tried to evaluate the charateristics of HSC in order to develop agents that inhibit hepatic fibrogenesis.
Extracellular Matrix/*metabolism ; Fibrosis ; Humans ; Liver/blood supply/metabolism/*pathology ; Liver Cirrhosis/etiology/genetics/*metabolism

No abstract available.
Extracellular Matrix/*metabolism ; Fibrosis ; Humans ; Liver/blood supply/metabolism/*pathology ; Liver Cirrhosis/etiology/genetics/*metabolism

BACKGROUNDUrethral reconstruction for both congenital and acquired etiologies remains a challenge for most urologic surgeons. Tissue engineering has been proposed as a strategy for urethral reconstruction. The purpose of this study was to determine whether a naturally derived extracellular matrix substitute developed for urethral reconstruction would be suitable for urethral repair in an animal model.

METHODSA urethral segmental defect was created in 20 male rabbits. The urethral extracellular matrix, obtained and processed from rabbit urethral tissue, was trimmed and transplanted to repair the urethral defect. Then, the regenerated segment was studied histologically by haematoxylin-eosin staining and Van Gieson staining at 10 days, 3 weeks, 6 weeks, and 24 weeks postoperation. Retrograde urethrography was used to evaluate the function of the regenerated urethras of 4 rabbits 10 and 24 weeks after the operation. The urodynamics of 4 rabbits from the experimental group and control group I were assessed and compared. In addition, 4 experimental group rabbits were examined by a urethroscope 24 weeks after the operation.

RESULTSAt 10 days after operation, epithelial cells had migrated from each side, and small vessels were observed in the extracellular matrix. The matrix and adjacent areas of the host tissue were infiltrated with inflammatory cells. The epithelium covered the extracellular matrix fully at 3 weeks postoperation. Well-formed smooth-muscle cells were first confirmed after 6 weeks, at which point the inflammatory cells had disappeared. At 24 weeks postoperation, the regenerated tissue was equivalent to the normal urethra. Urethrography and urodynamic evaluations showed that there was no difference between normal tissue and regenerated tissue.

CONCLUSIONSUrethral extracellular matrix appears to be a useful material for urethral repair in rabbits. The matrix can be processed easily and has good characteristics for tissue handling and urethral function.

Animals ; Extracellular Matrix ; metabolism ; Rabbits ; Tissue Engineering ; methods ; Urethra ; pathology ; surgery

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

OBJECTIVETo explore the relationship between the extracellular matrix and apoptosis of intestinal epithelium after burn injury.

METHODSThirty Wistar rats were employed in the study and were randomly divided into normal control (C) and 6 PBH (postburn hour), 12 PBH, 1 PBD (postburn day), 3 PBD and 5 PBD group with 5 rats in each group. The rats in burn groups were sacrificed at 0, 6 and 12 PBHs and 1, 3 and 5 PBDs. The apoptotic cell count and the caspases-3 activity of intestinal mucosal epithelium, and the extracellular matrix component laminin and type IV collagen were determined and their correlation was analyzed.

RESULTSThe apoptotic cell count and the caspases-3 activity of intestinal mucosal epithelium in burn groups were obviously higher than those in C group (P < 0.05 or 0.01), while the intestinal mucosal contents of laminin and type IV collagen in burned groups were much lower than those in C group (P < 0.05 or 0.01). By linear correlative analysis, it was shown that the changes in the intestinal mucosal contents of laminin and type IV collagen in burned groups were negatively correlated with the change in apoptotic cell count (r = -0.575, -0.613, P < 0.05).

CONCLUSIONIntestinal epithelial apoptosis was enhanced after burn injury, and it was correlated with the change in the components of the extracellular matrix.

Animals ; Apoptosis ; Burns ; metabolism ; pathology ; Caspase 3 ; metabolism ; Collagen Type IV ; metabolism ; Extracellular Matrix ; metabolism ; Female ; Intestinal Mucosa ; metabolism ; pathology ; Laminin ; metabolism ; Male ; Rats ; Rats, Wistar

OBJECTIVETo study the effects of oxymatrine (OM) on the expressions of pro-collagen I (PC I), pro-collagen II (PC III), fibronectin (FN), matrix metalloproteinase-1 (MMP-1) mRNA of fibroblasts from keloid (KFb), hyperplastic scar (HFb), and normal skin (NFb), and to compare with hydrocortisone (HC).

METHODSThe primary KFb, HFb and NFb were derived from patients and cultured in vitro using tissue block culture method. The fibroblasts were treated with 500 microg/mL OM, 2 microg/mL HC, or without any medicine (as the control). The mRNA expressions of PC I, PC III, FN, MMP-1 of the fibroblasts were detected using RT-PCR.

RESULTSUnder the normal condition, when compared with NFb, the mRNA expressions of PC I of KFb and HFb increased by 31.7% and 34.2% (both P < 0.05). Besides, the mRNA expression of PC III of KFb increased by 44.9% (P < 0.01). OM down-regulated the mRNA expressions of FN and PC I of HFb by 18.8% and 23.6% respectively (both P < 0.05). HC decreased the mRNA expressions of FN and PC I of HFb by 26.8% and 43.6% respectively (P < 0.05, P < 0.01). Meantime, OM up-regulated the mRNA expression of MMP-1 of KFb by 21.8% (P < 0.05).

CONCLUSIONSOM suppressed the synthesis of extracellular matrix (ECM) possibly through down-regulating the mRNA expressions of PC I and FN. Compared with HC, OM could promote the degradation of ECM through inducing the MMP-1 mRNA expressions of KFb. Therefore, OM could be potentially used in treatment of hypertrophic scar and keloid.

Alkaloids ; pharmacology ; Cells, Cultured ; Cicatrix ; metabolism ; pathology ; Extracellular Matrix ; metabolism ; pathology ; Fibroblasts ; drug effects ; metabolism ; pathology ; Fibronectins ; metabolism ; Humans ; Keloid ; metabolism ; pathology ; Matrix Metalloproteinase 1 ; metabolism ; Procollagen ; metabolism ; Quinolizines ; pharmacology

The reduction of extracellular matrix (ECM) degradation in kidney is taken as the morphological features and pathological base in renal injury in chronic kidney disease (CKD). ECM degradation is controlled by the catabolic enzyme systems in glomerulus and renal interstitium, in which matrix metalloproteinases (MMPs) play a key role. The expression and activity of MMPs are regulated by the classical pathway, such as the genic transcription, the activation of zymogen, and the specific inhibitor. The previous studies showed that, Uremic Clearance granule, as a representation, and other prescriptions of Chinese herbal medicine, as well as some extracts from Chinese herbal medicine could intervene the pathway of ECM degradation through promoting the degradation of ECM components, affecting the expression of catabolic enzymes, regulating the genetic transcription of MMPs, and inhibiting the relative signaling transduction of MMPs.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Matrix ; drug effects ; metabolism ; Humans ; Kidney ; cytology ; drug effects ; pathology ; Matrix Metalloproteinases ; metabolism ; Proteolysis ; drug effects ; Smad Proteins ; metabolism