Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor-beta (TGF-beta) is a cytokine that is important in embryogenesis, development, carcinogenesis, and tissue repair. TGF-beta is unique among cytokines in its widespread actions on the regulation of extracellular matrix. In a model of acute mesangial proliferative glomerulonephritis, it was shown that overproduction of TGF-beta is the cause of pathologic matrix accumulation in the nephritic glomeruli. TGF-beta acted to increase matrix production, inhibit matrix degradation, and modulate matrix receptors in the glomerulonephritic rats. Elevated expression of TGF-beta was also found in other experimental glomerular diseases, including diabetic nephropathy. Studies of humans with glomerulonephritis and diabetic nephropathy also strongly implicated TGF-beta in the pathogenesis of glomerular matrix build-up. Recently, the proteoglycan decorin was shown to neutralize TGF-beta. When injected into glomerulonephritic rats, decorin markedly suppressed pathologic matrix deposition in the glomeruli. Thus, decorin offers hope as a treatment for progressive kidney diseases caused by the overproduction of TGF-beta.
 ...
PMID:Transforming growth factor-beta and the pathogenesis of glomerular diseases. 785 Apr 12

Cytokines such as transforming growth factor-beta (TGF-beta) are peptide factors that regulate embryogenesis, development, inflammation, tissue repair, and carcinogenesis. Growing evidence indicates that dysregulation of cytokine actions may underlie the pathogenesis of serious autoimmune, degenerative, and fibrotic diseases. Studies in a model of acute mesangial proliferative glomerulonephritis show that overproduction of TGF-beta is the cause of pathologic accumulation of extracellular matrix in the nephritic glomeruli. Transforming growth factor-beta acts to increase matrix production, inhibit matrix degradation, and modulate matrix receptors in the glomerulonephritic rats. It may also play a role in the glomerular matrix build-up that is a central feature of diabetic nephropathy. Elevated expression of TGF-beta mRNA and TGF-beta protein were found in the glomeruli of diabetic rats along with increased levels of proteoglycans and other matrix components that are known to be induced by TGF-beta. The study of human diabetic glomeruli has also showed markedly elevated levels of TGF-beta protein. Glomeruli from normal kidneys and nonprogressive kidney disorders were negative. The striking ability of TGF-beta to cause exuberant matrix formation may be due to the fact that TGF-beta can induce its own production by resident cells at a site of injury. Thus, the potential for TGF-beta to do harm may be due to this autoinduction mechanism whereby TGF-beta expression can become chronic, creating a vicious circle. As the role that TGF-beta plays in chronic fibrotic diseases becomes better understood, it is likely that TGF-beta inhibitors will become important future drugs for treating these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cytokines in kidney disease: the role of transforming growth factor-beta. 832 71

MicroRNAs (miRNAs) are a family of small, noncoding RNAs that regulate gene expression in diverse biological and pathological processes, including cell proliferation, differentiation, apoptosis, and carcinogenesis. As a result, miRNAs emerged as major area of biomedical research with relevance to kidney fibrosis. Fibrosis is characterized by the excess deposition of extracellular matrix (ECM) components, which is the end result of an imbalance of metabolism of the ECM molecule. Recent evidence suggests that miRNAs participate in the fibrotic process in a number of organs including the heart, kidney, liver, and lung. Epithelial mesenchymal transition (EMT) and endothelial mesenchymal transition (EndMT) programs play vital roles in the development of fibrosis in the kidney. A growing number of the extracellular and intracellular molecules that control EMT and EndMT have been identified and could be exploited in developing therapeutics for fibrosis. This review highlights recent advances on the role of miRNAs in the kidney diseases; diabetic nephropathy especially focused on EMT and EndMT program responsible for the development of kidney fibrosis. These miRNAs can be utilized as a potential novel drug target for the studying of underlying mechanism and treatment of kidney fibrosis.
...
PMID:MicroRNAs in kidney fibrosis and diabetic nephropathy: roles on EMT and EndMT. 2408 59