| Diabetic nephropathy, DN is one of the Diabetic chronic complications, it is the main reason for disability and death caused by diabetes mellitus (DM). According to statistics, 30 percent to 40 percent of the type I diabetes patients and 40 percent of the type II diabetes patients with diabetic nephropathy, there may be proteinuria hypertension at the first to the development of nephrotic syndrome, leading to renal failure and death, the 3 year survival rate of DN is only about 50 percent. Glucose metabolism in the polyol pathway is closely related to diabetic chronic complications such as diabetic vascular disease, kidney disease, retinopathy and peripheral neuropathy. And aldose reductase is a polyol sugar metabolism speed of the slip road, therefore, increased AR activity may be one of the main reasons leading to DN.Aldose reductase is one of the two enzymes composed of polyol pathway, which is also the speed limit enzyme of the glucose metabolism , responsible for the reduction of glucose to sorbitol with the help of supporting factor NADPH. In renal, AR is highly expressed at inner medulla, in order to convert glucose to sorbitol. The latter is the important organic osmolyte in kidney, used to protect the renal collection tubule cell out of the damage caused by high osmotic pressure.Sustained high blood glucose is the major risk factors lesd to diabetic nephropathy, high blood glucose can lead mesangial matrix expansion and mesangial cell proliferation through certain serine / threonine protein kinase .Serum and glucocorticoid inducible protein kinase, SGK is a novel member of the serine/threonine protein kinase gene family, which has SGK1, SGK2 and SGK3 3 subtypes. Unlike the vast majority of protein kinases, which are predominantly regulated at the enzymatic level by posttranslational phosphorylation and dephosphorylation, the transcript expression, activity and subcellular localization of SGK1 can be acutely controlled by a diverse set of stimuli. SGK is an important focal point of intracellular cross-talk to control many cellular processes, including cell proliferation, osmoregulation, ion channel regulation and cell survival and/or apoptotic responses. The expression of SGK1 mRNA in diabetic patients kidney was significantly higher than normal, thus SGK1 may be involved in the incidence of diabetic nephropathy.The sodium/potassium/2 chloride cotransporter type 2 (NKCC2) is located in the apical membrane of the thick ascending limb (TAL) and macula densa,which has NKCC2A, NKCC2B and NKCC2F 3 subtypes.NKCC2 is involved in the active transport of sodium from the lumen into the basolateral fluid. As a result, salt accumulates in the medullary interstitium. Hypertonicity in the medullary interstitium created by the high concentration of salt is an important local signal for the renal medulla.However, the research on the relation between AR,NKCC2 and SGK1 has not reported so far. We constructed a adenovirus with mouse AR,NKCC2 gene and infected into mIMCD3 cells, then research on the relationship between AR,NKCC2 and SGK1 using western blot and immunocytochemical technology. The results showed that: in vitro ,after over- expression of the AR, the expression of SGK1 has been significantly improved in mIMCD3 cells. In addition, by means of immunohistochemistry ,we also found that the SGK1 expression decreased significantly in the kidney of AR-knockout mouse, and there was some restoration of SGK1 expression in the kidney of AR bitransgenic mice. Note that the expression of SGK1 in renal cells is positive regulated by AR.
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