So far, the cornerstone therapy of DN consists of renin-angiotensin system (RAS) inhibitors, agents that decrease the synthesis of intrarenal angiotensin II or block its receptors.
The anti-DN benefit of vitamin D can be enhanced when administrated in combination with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers.
Angiotensin II, reactive oxygen species, and other factors in the setting of DKD stimulate drastic increases in calcium influx through the TRPC6 channel, causing podocyte hypertrophy and foot process effacement.
The intrarenal renin-angiotensin system, in particular augmentation of angiotensinogen (AGT) in proximal tubular cells (PTC), plays a crucial role in the development of diabetic nephropathy.
These data indicate that increasing AcSDKP by blocking the ACE N-domain facilitates sodium excretion and ameliorates diabetic kidney disease independent of intrarenal angiotensin II regulation.
Microvascular complications were graded as follows: neuropathy by clinical assessment, electrophysiology, vibration and cooling detection thresholds, heart rate variability, and corneal confocal microscopy; retinopathy by ultra-wide-field retinal imaging; and DKD by renal hemodynamic function measured by inulin and para-aminohippurate clearance at baseline and after intravenous infusion of angiotensin II.
Comprehensive electronic search in Pubmed, Web of Science, EBSCO, Embase, the Cochrane Library and China National Knowledge Infrastructure (CNKI) to find original articles about the association between AGTM235T polymorphism and DN risk published before 27 September 2017.
This study is a continuation of our previous research on the association between angiotensinogen (AGT) gene polymorphisms and DN in patients with T2DM.
Although the diabetic milieu per se , hemodynamic changes, oxidative stress and local growth factors such as angiotensin II (AII) are considered to be mediators in the pathogenesis of diabetic nephropathy, the underlying pathways mediating the changes in glomerular endothelial cells (GECs) are not well understood.
It is noteworthy that the efferent glomerular arteriole is 10 - 100 times more sensitive to the vasoconstrictive properties of angiotensin II than the afferent one and this might account for the consequently higher intra-glomerular capillary pressure, which is believed to be the cornerstone of diabetic nephropathy.
The present study has demonstrated, for the first time, that high glucose augments AGT in human RPTCs through HNF-5, which provides a potential therapeutic target for diabetic nephropathy.
The effects of some RAAS gene variants, including angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R), on the risk for DN have been studied more extensively, but there has been controversy.
Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and recognized to be renoprotective by degrading Angiotensin II to Angiotensin (1-7) in diabetic nephropathy.
These data suggest that the augmented angiotensinogen mRNA levels in segment 3 and angiotensinogen protein levels in segments 1 and 3 may contribute to the progression of diabetic nephropathy.
Although key signal transduction and gene regulation mechanisms have been identified, especially those related to the effects of hyperglycaemia, transforming growth factor β1 and angiotensin II, progress in functional genomics, high-throughput sequencing technology, epigenetics and systems biology approaches have greatly expanded our knowledge and uncovered new molecular mechanisms and factors involved in DN.
Gene-gene interaction between acetyl-coenzymeA carboxylase beta (ACACβ) gene, which is involved in fatty acid metabolism and angiotensin II receptors (AGTR1) gene, which mediates RAS proteins actions on renal tissue, polymorphism with DN have not been studied earlier.