Transforming growth factor-beta/connective tissue growth factor axis in the kidney.
Transforming growth factor-beta(1) (TGFbeta(1)) is recognized as both a fibrogenic and inflammatory cytokine and plays a critical role in the kidney pathophysiology. The dysregulation of TGFbeta(1) has been linked with the development of diabetic nephropathy. Connective tissue growth factor (CTGF) is a fibrogenic cytokine and is recognized as a downstream mediator of TGFbeta(1) in kidney fibrosis. TGFbeta(1) is involved in immunomodulation and fibrosis in the kidney. However, CTGF plays a more specific role in the fibrogenic pathways in the kidney proximal tubule cells. Moreover, CTGF facilitates TGFbeta(1) signaling and promotes renal fibrosis. This suggests CTGF could be a potential target for kidney fibrosis. Long-term inhibition and targeting TGFbeta(1) directly is problematic, therefore, a more fruitful direction targeting diabetic nephropathy may involve the development of therapeutic strategies specifically targeting CTGF.
Qi
Weier
W
Department of Medicine, University of Sydney, Level 3, Wallace Freeborn Professorial Block, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.
Chen
Xinming
X
Poronnik
Philip
P
Pollock
Carol A
CA
D000818:Animals; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D051379:Mice; D023421:Models, Animal; D051381:Rats; D015398:Signal Transduction; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D051896:Smad Proteins, Receptor-Regulated; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor