scholarly journals Cell division autoantigen 1 enhances signaling and the profibrotic effects of transforming growth factor-β in diabetic nephropathy

2011 ◽  
Vol 79 (2) ◽  
pp. 199-209 ◽  
Author(s):  
Yugang Tu ◽  
Tieqiao Wu ◽  
Aozhi Dai ◽  
Yen Pham ◽  
Phyllis Chew ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Cell Division ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Transforming Growth Factor-β–Induced Cross Talk Between p53 and a MicroRNA in the Pathogenesis of Diabetic Nephropathy

Diabetes ◽  
2013 ◽  
Vol 62 (9) ◽  
pp. 3151-3162 ◽  
Author(s):  
Supriya D. Deshpande ◽  
Sumanth Putta ◽  
Mei Wang ◽  
Jennifer Y. Lai ◽  
Markus Bitzer ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Cross Talk ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Receptor-mediated nonproteolytic activation of prorenin and induction of TGF-β1 and PAI-1 expression in renal mesangial cells

2012 ◽  
Vol 303 (1) ◽  
pp. F11-F20 ◽  
Author(s):  
Jiandong Zhang ◽  
Jie Wu ◽  
Chunyan Gu ◽  
Nancy A. Noble ◽  
Wayne A. Border ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Plasminogen Activator Inhibitor ◽  
Transforming Growth Factor Β ◽  
Diabetic Patients ◽  
Ang Ii ◽  
Plasminogen Activator Inhibitor 1 ◽  
Pai 1

While elevated plasma prorenin levels are commonly found in diabetic patients and correlate with diabetic nephropathy, the pathological role of prorenin, if any, remains unclear. Prorenin binding to the (pro)renin receptor [(p)RR] unmasks prorenin catalytic activity. We asked whether elevated prorenin could be activated at the site of renal mesangial cells (MCs) through receptor binding without being proteolytically converted to renin. Recombinant inactive rat prorenin and a mutant prorenin that is noncleavable, i.e., cannot be activated proteolytically, are produced in 293 cells. After MCs were incubated with 10−7 M native or mutant prorenin for 6 h, cultured supernatant acquired the ability to generate angiotensin I (ANG I) from angiotensinogen, indicating both prorenins were activated. Small interfering RNA (siRNA) against the (p)RR blocked their activation. Furthermore, either native or mutant rat prorenin at 10−7 M alone similarly and significantly induced transforming growth factor-β1, plasminogen activator inhibitor-1 (PAI-1), and fibronectin mRNA expression, and these effects were blocked by (p)RR siRNA, but not by the ANG II receptor antagonist, saralasin. When angiotensinogen was also added to cultured MCs with inactive native or mutant prorenin, PAI-1 and fibronectin were further increased significantly compared with prorenin or mutant prorenin alone. This effect was blocked partially by treatment with (p)RR siRNA or saralasin. We conclude that prorenin binds the (p)RR on renal MCs and is activated nonproteolytically. This activation leads to increased expression of PAI-1 and transforming growth factor-β1 via ANG II-independent and ANG II-dependent mechanisms. These data provide a mechanism by which elevated prorenin levels in diabetes may play a role in the development of diabetic nephropathy.

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