Involvement of the growth hormone (GH) / insulin-like growth factor 1 (IGF-1) axis in the pathogenesis of diabetic nephropathy (DN) is strongly suggested by studies investigating the impact of GH excess and deficiency on renal structure and function. GH excess in both the human (acromegaly) and in transgenic animal models is characterized by significant structural and functional changes in the kidney. In the human a direct relationship has been noted between the activity of the GH/IGF-1 axis and renal hypertrophy, microalbuminuria, and glomerulosclerosis. Conversely, states of GH deficiency or deficiency or inhibition of GH receptor (GHR) activity confer a protective effect against DN. The glomerular podocyte plays a central and critical role in the structural and functional integrity of the glomerular filtration barrier and maintenance of normal renal function. Recent studies have revealed that the glomerular podocyte is a target of GH action and that GHs actions on the podocyte could be detrimental to the structure and function of the podocyte. These results provide a novel mechanism for GHs role in the pathogenesis of DN and offer the possibility of targeting the GH/IGF-1 axis for the prevention and treatment of DN.
Keywords: Growth hormone, Podocyte, Diabetic nephropathy, Review, hypothalamic factors GHRH, somatostatin, Pituitary, GH receptor (GHR), GH binding protein (GHBP), Janus kinase, signal transducer and activator, mitogen-activated protein, phosphoinositide 3-kinase, blastocyst, colonic epithelial cells, cardiomyo-cytes, glomerular podocyte, insulin-like growth, IGF binding proteins (IGFBPs), acid labile, iabetes mellitus, ESRD, GHR, IGF-1, hIGF-1, streptozotocin, G120K-polyethylene glycol, JAK-2 adapter protein, focal adhesion kinase, reactive oxygen species, SH2-B, integrin-linked, ILK induction, serine threonine, catenin/LEF, metalloproteinase-9, SIP1/ZEB2, EF-1, SIP1 inhibits E-cadherin expression, E-cadherin, pegvisomant, GFR
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