Cellular crosstalk of glomerular endothelial cells and podocytes in diabetic kidney disease

Abstract

Diabetic kidney disease (DKD) is a serious microvascular complication of diabetes and is the leading cause of end-stage renal disease (ESRD). Persistent proteinuria is an important feature of DKD, which is caused by the destruction of the glomerular filtration barrier (GFB). Glomerular endothelial cells (GECs) and podocytes are important components of the GFB, and their damage can be observed in the early stages of DKD. Recently, studies have found that crosstalk between cells directly affects DKD progression, which has prospective research significance. However, the pathways involved are complex and largely unexplored. Here, we review the literature on cellular crosstalk of GECs and podocytes in the context of DKD, and highlight specific gaps in the field to propose future research directions. Elucidating the intricates of such complex processes will help to further understand the pathogenesis of DKD and develop better prevention and treatment options.

Keywords: Cellular crosstalk; Diabetic kidney disease; Glomerular endothelial cell; High glucose; Podocyte.

Fig. 1

Cellular crosstalk of glomerular endothelial cells. (TGF-β, transforming growth factor-β; HGF, hepatocyte growth factor; c-Met, c-mesenchymal-epithelial transition factor; FAT, fatty acid translocase; LRG-1, leucine-rich α-2-glycoprotein 1; PDGFB, platelet-derived growth factor B; PDGFRβ, platelet-derived growth factor receptor β; APC, activated protein C; PAR-3, protease activated receptor-3; KLF2, Kruppel -like factor 2; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; VEGF, vascular endothelial growth factor; Smad, small mother against decapentaplegic; Wnt, Wingless and Int-1;)

Fig. 2

Cellular crosstalk of VEGF produced by podocyte in DKD. (DKD, diabetic kidney disease; VEGF-A, vascular endothelial growth factor A; VEGF-B, vascular endothelial growth factor B; VEGFR-1, vascular endothelial growth factor receptor 1; VEGFR-2, vascular endothelial growth factor receptor 2;)

Fig. 3

Ang-1 and Ang-2 in DKD. (Ang1, angiopoietin 1; Ang2, angiopoietin 2; Tie-2, tyrosine kinase receptor-2;)

Fig. 4

Cellular crosstalk of podocytes. (HB-EGF, heparin-binding epidermal growth factor-like growth factor; CCN2, cellular communication network factor 2; ET, endothelin; CXCR4, CXC chemokine receptor 4; SDF-1, stromal cell-derived factor-1; Ang1, angiopoietin 1; Tie-2, angiopoietin receptor-2; MCP-1, monocyte chemotactic protein 1; CCR2, C–C chemokine receptor type 2; VEGFR-1, vascular endothelial growth factor receptor 1; VEGF-B, vascular endothelial growth factor B; VEGFR-2, vascular endothelial growth factor receptor 2; VEGF-A, vascular endothelial growth factor A; CCL21, C–C chemokine ligand 21; CCR7, C–C chemokine receptor type 7;)

Fig. 5

Cellular crosstalk of endothelial cells and podocytes in diabetic kidney disease. (HB-EGF, heparin-binding epidermal growth factor-like growth factor; TGF-β, transforming growth factor-β; HGF, hepatocyte growth factor; FAT, fatty acid translocase; LRG-1, leucine-rich α-2-glycoprotein 1; PDGFB, platelet-derived growth factor B; APC, activated protein C; KLF2, Kruppel -like factor 2; eNOS, endothelial nitric oxide synthase; VEGF-A, vascular endothelial growth factor A; VEGF-B, vascular endothelial growth factor B; MCP-1, monocyte chemotactic protein 1; ET-1, endothelin-1; SDF-1, stromal cell-derived factor-1; Ang, angiopoietin; CCL21, C–C chemokine ligand 21; CCN2, cellular communication network factor 2;)