ALK1-Smad1/5 signaling pathway in fibrosis development: friend or foe?
Fibrosis is a common phenomenon associated with several pathologies, characterized by an excessive extracellular matrix deposition that leads to a progressive organ dysfunction. Thus fibrosis has a relevant role in chronic diseases affecting the kidney, the liver, lung, skin (scleroderma) and joints (arthritis), among others. The pathogenesis of fibrosis in different organs share numerous similarities, being one of them the presence of activated fibroblasts, denominated myofibroblast, which act as the main source of extracellular matrix proteins. Transforming growth factor beta-1 (TGF-β1) is a profibrotic cytokine that plays a pivotal role in fibrosis. The TGF-β1/ALK5/Smad3 signaling pathway has been studied in fibrosis extensively. However, an increasing number of studies involving the ALK1/Smad1 pathway in the fibrotic process exist. In this review we offer a perspective of the function of ALK1/Smad1 pathway in renal fibrosis, liver fibrosis, scleroderma and osteoarthritis, suggesting this pathway as a powerful therapeutical target. We also propose several strategies to modulate the activity of this pathway and its consequences in the fibrotic process.
Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain; Biomedical Research Institute of Salamanca (IBSAL), 37007 Salamanca, Spain; Institute Queen Sophie for Renal Research, 37007 Salamanca, Spain.
José M
JM
Muñoz-Félix
María
M
González-Núñez
José M
JM
López-Novoa
D030301:Activin Receptors, Type II / Q000378:metabolism*; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D051898:Smad1 Protein / Q000378:metabolism*; D051902:Smad5 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D051898:Smad1 Protein; D051902:Smad5 Protein; D016212:Transforming Growth Factor beta; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II
Cirrhosis; Collagen; Extracellular matrix; Fibrosis; Smad