Hepatic fibrosis is a reparative response of diffuse over deposition and abnormal distribution of extracellular matrix (collagen, glycoprotein and proteoglycans) after exposure to various kinds of liver injuries, and is a key step in the developmental process of various chronic liver diseases to cirrhosis. Recently, many advances in our understanding of hepatic fibrosis have been recognized through the basic and clinical research. Therefore, we have organized the relevant domestic experts of this field to form consensus on the diagnosis and evaluation, treatment, and clinical development and application of therapy in order to better guide the diagnosis and treatment, and drug research and development.
Consensus ; Extracellular Matrix/pathology* ; Humans ; Liver/pathology* ; Liver Cirrhosis/therapy*

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

The classification as well as the clinical manifestations of hereditary malformations of dentin are of great concern and have been deeply elucidated. The understanding of its genetic basis also increases progressively. Dentin sialophosphoprotein (DSPP) is the pathogenic gene of dentinogenesis imperfecta type Ⅱ, dentinogenesis imperfecta type Ⅲ and dentin dysplasia type Ⅱ. In this article, the classification of DSPP mutations as well as the resultant dysfunction of the mutant DSPP are summarized respectively and the corresponding clinical manifestations are analyzed. This work will provide a reference for the diagnosis and treatment of hereditary malformations of dentin.
Humans ; Dentinogenesis Imperfecta/pathology* ; Mutation ; Extracellular Matrix Proteins/genetics* ; Phosphoproteins/genetics* ; Sialoglycoproteins/genetics* ; Dentin/pathology*

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

Carious lesions are bacteria-caused destructions of the mineralised dental tissues, marked by the simultaneous activation of immune responses and regenerative events within the soft dental pulp tissue. While major molecular players in tooth decay have been uncovered during the past years, a detailed map of the molecular and cellular landscape of the diseased pulp is still missing. In this study we used single-cell RNA sequencing analysis, supplemented with immunostaining, to generate a comprehensive single-cell atlas of the pulp of carious human teeth. Our data demonstrated modifications in the various cell clusters within the pulp of carious teeth, such as immune cells, mesenchymal stem cells (MSC) and fibroblasts, when compared to the pulp of healthy human teeth. Active immune response in the carious pulp tissue is accompanied by specific changes in the fibroblast and MSC clusters. These changes include the upregulation of genes encoding extracellular matrix (ECM) components, including COL1A1 and Fibronectin (FN1), and the enrichment of the fibroblast cluster with myofibroblasts. The incremental changes in the ECM composition of carious pulp tissues were further confirmed by immunostaining analyses. Assessment of the Fibronectin fibres under mechanical strain conditions showed a significant tension reduction in carious pulp tissues, compared to the healthy ones. The present data demonstrate molecular, cellular and biomechanical alterations in the pulp of human carious teeth, indicative of extensive ECM remodelling, reminiscent of fibrosis observed in other organs. This comprehensive atlas of carious human teeth can facilitate future studies of dental pathologies and enable comparative analyses across diseased organs.
Humans ; Dental Pulp ; Fibronectins ; Extracellular Matrix/pathology* ; Dental Caries ; Sequence Analysis, RNA

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

Fibrosis can occur in different organs with high incidence rate and great danger. It still lacks effective drugs for prevention of fibrosis. Fluorofenidone is a newly developed drug with anti-fibrotic activity, which provides a new hope for treating the progressive fibrotic diseases. Recent studies have shown that fluorofenidone is a multifunctional small molecule with anti-inflammatory, antioxidative and anti-apoptotic eff ects. It can inhibit the activation and proliferation of myofibroblasts, promote the degradation of extracellular matrix and regulate the cellular signal transmission. Fluorofenidone can be applied to attenuate the progression of renal, hepatic and pulmonary fibrosis.
Apoptosis ; Extracellular Matrix ; Fibrosis ; Humans ; Kidney ; pathology ; Liver Cirrhosis ; Pulmonary Fibrosis ; Pyridones ; pharmacology ; Signal Transduction

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.