| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 cell biology,endocrinology, university of oklahoma, oklahoma city, Oklahoma, United States
2 Ophthalmology, university of oklahoma, oklahoma city, Oklahoma, United States
3 Univ Oklahoma, United States; Ophthalmology, Univ Oklahoma, United States
4 Cell Biology, Medicine, Univ. of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
* To whom correspondence should be addressed. E-mail: jian-xing-ma{at}ouhsc.edu.
Previously, we have reported that pigment epithelium-derived factor (PEDF) ameliorates albuminuria and inhibits matrix protein deposition in the kidney of streptozotocin (STZ)-induced diabetic rats, suggesting a reno-protective effect of PEDF in early stages of diabetic nephropathy. As inflammation is a major contributor to the development and progression of diabetic nephropathy, we examined in the present study whether PEDF inhibits renal inflammation in diabetic kidney. Diabetic rats received an intravenous injection of adenovirus expressing PEDF (Ad-PEDF) or the same titer of a control virus. Three weeks after the injection, diabetic rats treated with the control virus showed significantly elevated renal levels of pro-inflammatory factors such as ICAM-1, MCP-1, TNF-
and VEGF when compared with age-matched non-diabetic controls. Ad-PEDF effectively suppressed the over-expression of these pro-inflammatory factors in diabetic kidneys. In cultured primary human renal mesangial cells (HMC), the high glucose medium-induced up-regulation of VEGF and MCP-1 was largely blocked by PEDF. Furthermore, PEDF inhibited high glucose-induced activation of NF-
B, a key transcription factor mediating inflammatory responses, and HIF-1, a major activator of VEGF expression in HMC. These results suggest that the reno-protective effect of PEDF against diabetic nephropathy may be partially through its anti-inflammatory activity, likely by blocking the NF-B and HIF-1 pathways.
This article has been cited by other articles:
|
|
 |
|
  C. Zhang, Y. Tan, W. Guo, C. Li, S. Ji, X. Li, and L. Cai Attenuation of diabetes-induced renal dysfunction by multiple exposures to low-dose radiation is associated with the suppression of systemic and renal inflammation Am J Physiol Endocrinol Metab, December 1, 2009; 297(6): E1366 - E1377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nasu, Y. Maeshima, M. Kinomura, K. Hirokoshi-Kawahara, K. Tanabe, H. Sugiyama, H. Sonoda, Y. Sato, and H. Makino Vasohibin-1, a Negative Feedback Regulator of Angiogenesis, Ameliorates Renal Alterations in a Mouse Model of Diabetic Nephropathy Diabetes, October 1, 2009; 58(10): 2365 - 2375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Good, T. George, and B. A. Watts III Lipopolysaccharide directly alters renal tubule transport through distinct TLR4-dependent pathways in basolateral and apical membranes Am J Physiol Renal Physiol, October 1, 2009; 297(4): F866 - F874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakagawa, T. Kosugi, M. Haneda, C. J. Rivard, and D. A. Long Abnormal Angiogenesis in Diabetic Nephropathy Diabetes, July 1, 2009; 58(7): 1471 - 1478. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
