The renin inhibitor aliskiren attenuates high glucose-induced extracellular matrix and prevents apoptosis in cultured podocytes
by Phillips, Lynetta M., M.S., CALIFORNIA STATE UNIVERSITY, DOMINGUEZ HILLS, 2008, 24 pages; 1455384

Abstract:

Diabetic nephropathy (DN) is partially characterized by altered extracellular matrix (ECM) remodeling and podocyte death. Aliskiren (ALI) inhibits the renin-catalyzed conversion of angiotensinogen to angiotensin I. This study tested ALI's effect on podocyte ECM accretion and survival in high glucose conditions.

Conditionally immortalized mouse podocytes were incubated in normal glucose (NG, 5.5mM) or high glucose (HG, 40mM) for 24-48 hours with and without ALI (20nM). Real-time RT-PCR was performed for fibronectin (FN), alpha5(IV) collagen (cola5IV), matrix metalloproteinases (MMP2, MMP9), and tissue inhibitor of metalloproteinases (TIMP1, TIMP2). Immunoblots were performed for FN, cola5IV, MMP2, TIMP1 and cleaved caspase-3 (CC3).

ALI significantly reduced FN protein, cola5IV mRNA and protein, TIMP1 protein and CC3; had no effect on MMP2 mRNA or protein or TIMP2 mRNA; and increased MMP9 mRNA.

Renin inhibition with ALI mitigates the profibrotic and apoptotic effects of HG in podocytes. These data strengthen the rationale for ALI administration in DN.

 
Advisor
SchoolCALIFORNIA STATE UNIVERSITY, DOMINGUEZ HILLS
SourceMAI/ 46-06, p. , Aug 2008
Source TypeThesis
SubjectsMolecular biology; Cellular biology
Publication Number1455384
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