|Year : 2014 | Volume
| Issue : 2 | Page : 51-52
Glomerular Capillary Endothelial Injury in Diabetic Nephropathy
Dingkun Gui, Niansong Wang
Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China
|Date of Web Publication||27-Oct-2014|
Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai - 200 233
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gui D, Wang N. Glomerular Capillary Endothelial Injury in Diabetic Nephropathy. J Integr Nephrol Androl 2014;1:51-2
In the first issue of the Journal of Integrative Nephrology and Andrology, Huang et al. investigated the changes in the level of adiponectin (ADPN) and CD146 in serum in patients with type 2 diabetic nephropathy (DN) and found that serum ADPN and CD146 may protect against vascular endothelial dysfunction in DN. This is an important and interesting topic. Given the important role the endothelium plays in both the development and the progression of DN, further study needs to be performed to develop effective strategies that prevent its loss or promote its regeneration. Such advances may not only improve tissue oxygenation and reduce fibrosis, but also improve long-term renal function. Thus, we will further discuss the important role of glomerular capillary endothelial dysfunction in the pathogenesis and progression of DN.
Increasing evidence indicates that hyperglycemia-mediated endothelial injury may predispose to albuminuria in diabetes through direct effects and interaction with podocytes. In 1989, Jensen et al., first reported that endothelial injury was present in patients with incipient type 1 diabetes and endothelial function was more obviously impaired in overt nephropathy patients than those incipient nephropathy patients. It is now clear that the endothelium plays an important part of the glomerular barrier and epithelial dysfunction plays a pivotal role in the development of DN.  Glomerular endothelial cell (GEnC) fenestrations are specialized for their important role as a prerequisite for filtration across the glomerular capillary wall. Glomerular filtration rate is dependent on the fractional area of the fenestrations and GEnC fenestrations play a critical role in restriction of protein loss. Hence, dysregulation of GEnC fenestrations may be related to both renal fuction loss and proteinuria. However, their important role in the glomerular filtration barrier has not received full attention. In the renal microcirculation, both arterioles and GEnCs have been implicated as targets of hyperglycemia-induced injury. Both hyperglycemia per se and the metabolic consequences of high glucose are thought to cause endothelial cell dysfunction. The impaired GEnCs may then function as active signal transducers of metabolic, hemodynamic and inflammatory factors that modify the function and morphology of the vessel wall and interact with neighboring cells, which may activate a cascade of proliferative and inflammatory responses in the development of DN. It has been reported that high glucose could cause activation of the local renin-angiotensin system in GEnCs.  In vivo study further demonstrated that injury to the glomerular endothelial surface layer might play an important role in the pathogenesis of albuminuria in rats with early-stage diabetes.  Huang et al. suggest that ADPN is an important marker of endothelial cell injury in individuals with DN. The low level of serum ADPN may affect endothelial dysfunction in DN. Therefore, glomerular capillary endothelial dysfunction plays a crucial role in the pathogenesis and development of DN.
Moreover, GEnC can interact with neighboring podocytes. A previous study confirmed the important role of podocyte detachment and diminished endothelial cell fenestration in the development and progression of kidney disease in type 2 diabetes.  Krüppel-like factor 2 (KLF2) was reported to play an important role in GEnC injury in the early stage of DN and podocyte injury was more severe in diabetic knockout compared with diabetic wild-type mice, indicating a crosstalk between GEnC and podocytes.  A recent study demonstrated that the combined effects of endothelial nitric oxide synthase (eNOS) deficiency and hyperglycemia induced podocyte injury, indicating the important role of communication between endothelial cells and podocytes in diabetes. 
Based on the above-mentioned studies, further study is required to investigate the podocyte/glomerular basement membrane (GBM) adherence and podocyte/endothelial cell functional interactions in DN, which may provide a potential new therapeutic option for the treatment of DN.
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