The role of gene Dapper1 a Wnt pathway inhibitor, in apoptosis triggered by TGF-beta in mesangial cells

• Grant number: 12/08133-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2012
• End date: December 31, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Alexandre Holthausen Campos
• Grantee: Daniele Pereira Jardim
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

Diabetic nephropathy is a leading cause of end-stage renal disease, which is associated with high morbidity and mortality rates. Factors and mechanisms involved in renal injury due to diabetes are complex and poorly understood. TGF-b1, a cytokine which regulates the expression of different classes of genes, induces phenotypic modifications in glomerular cells. Recent data from our laboratory confirm that TGF-b1 mediates apoptosis in mesangial cells. Molecular mechanisms associated to this phenomenon are yet to be defined. Previous data from our group identified Dapper1 gene upregulation in response to TGF-b1 in cultured human mesangial cells. It is known that Dapper1 negatively regulates the WNT pathway, positively associated with cell survival; in addition, recent work demonstrated that Wnt is able to block apoptosis in mesangial cells exposed to high ambient glucose. We hypothesized that Dapper1 is a direct mediator TGF-b1-induced mesangial cell death. Our preliminary results demonstrate that Dapper1 overexpression increases apoptosis in mesangial cells, suggesting that this gene may be an important player in the pathophysiology of diabetic nephropathy. (AU)