Abstract
Aim
We examined the role of Nox5 in human diabetic nephropathy (DN), in human renal cell populations and in a high fat fed rabbit model of kidney disease.
Background
Oxidative stress plays an important role in mediating kidney injury in diabetes. Evidences suggest that pro-oxidant enzyme, Nox5 plays a significant role in human DN. Nox5 is present in humans and rabbits but not in mice or rats. Thus, there is a paucity of information about Nox5 in conventional animal models of DN.
Methods
Protein expression of Nox5 was examined by immunostaining in human kidney biopsies obtained from non-diabetic and diabetic individuals. In vitro, Nox5 was silenced in human mesangial cells, podocytes and in proximal tubules and were exposed to high glucose, TGF-β and AngII. Cell morphology, gene and protein expression of markers of fibrosis and inflammation and the level of ROS were assessed. We also examined expression of pro-fibrotic gene in high fat fed rabbits by next generation sequencing (NGS) and renal injury by histochemistry.
Results
Expression of Nox5 was increased in both glomerular and tubular compartments of kidney biopsies obtained from diabetic versus non-diabetic individuals. Silencing of Nox5 resulted in reduced ROS production and decreased expression of pro-fibrotic and pro-inflammatory markers as well as putative elements that are implicated in DN. Moreover, increased expression of Nox5 in high fat fed rabbits versus normal diet fed rabbits was associated with increased expression of fibronectin, CTGF, collagen IV and VCAM-1 and increased mesangial expansion in the kidney.
Conclusions
Collectively, these findings suggest that Nox5 derived ROS accelerates renal injury in diabetes and provide proof of principle for the development of a new renoprotective agent in diabetes.
We examined the role of Nox5 in human diabetic nephropathy (DN), in human renal cell populations and in a high fat fed rabbit model of kidney disease.
Background
Oxidative stress plays an important role in mediating kidney injury in diabetes. Evidences suggest that pro-oxidant enzyme, Nox5 plays a significant role in human DN. Nox5 is present in humans and rabbits but not in mice or rats. Thus, there is a paucity of information about Nox5 in conventional animal models of DN.
Methods
Protein expression of Nox5 was examined by immunostaining in human kidney biopsies obtained from non-diabetic and diabetic individuals. In vitro, Nox5 was silenced in human mesangial cells, podocytes and in proximal tubules and were exposed to high glucose, TGF-β and AngII. Cell morphology, gene and protein expression of markers of fibrosis and inflammation and the level of ROS were assessed. We also examined expression of pro-fibrotic gene in high fat fed rabbits by next generation sequencing (NGS) and renal injury by histochemistry.
Results
Expression of Nox5 was increased in both glomerular and tubular compartments of kidney biopsies obtained from diabetic versus non-diabetic individuals. Silencing of Nox5 resulted in reduced ROS production and decreased expression of pro-fibrotic and pro-inflammatory markers as well as putative elements that are implicated in DN. Moreover, increased expression of Nox5 in high fat fed rabbits versus normal diet fed rabbits was associated with increased expression of fibronectin, CTGF, collagen IV and VCAM-1 and increased mesangial expansion in the kidney.
Conclusions
Collectively, these findings suggest that Nox5 derived ROS accelerates renal injury in diabetes and provide proof of principle for the development of a new renoprotective agent in diabetes.
| Original language | English |
|---|---|
| Pages (from-to) | 34 |
| Number of pages | 1 |
| Journal | Nephrology |
| Volume | 22 |
| Issue number | S3 |
| Publication status | Published - Sept 2017 |
| Event | Annual Scientific Meeting of the Australian-and-New-Zealand-Society-of-Nephrology 2017 - Darwin Convention Centre, Darwin, Australia Duration: 4 Sept 2017 → 6 Sept 2017 Conference number: 53rd https://onlinelibrary.wiley.com/toc/14401797/2017/22/S3 (Nephrology Vol 22, Issue S3) |
