Angiopoietin-like protein 4 dysregulation in kidney diseases: a promising biomarker and therapeutic target

Figures

• 

  FIGURE 1. Schematic representation of the ANGPTL1-8 structure. The ANGPTL family typically comprises three conserved structural domains: the signal peptide (SP, blue), the coiled-coil domain (CCD, green), and the fibrinogen-like domain (FLD, red). However, ANGPTL8 is an exception, as it lacks the C-terminal FLD.

• 

  FIGURE 2. Structure and function of ANGPTL4. ANGPTL4 is composed of several distinct regions: the signal peptide, the N-terminal coiled-coil domain (nANGPTL4, 15 kDa), the linker region, and the C-terminal fibrinogen-like domain (cANGPTL4, 35 kDa). The glycosylated secretory protein (fANGPTL4, 45–65 kDa) undergoes proteolytic cleavage by proprotein convertases (including PCSK3, Furin, and PC5/6) at the amino acid sequence R161RKR164, as indicated by the scissor symbol. After cleavage, the ANGPTL4 domains are released from the cell, with nANGPTL4 remaining in an oligomeric state and cANGPTL4 dissociating into monomers. nANGPTL4 plays a crucial role in lipid metabolism, whereas cANGPTL4 is involved in several nonlipid-related processes. Created with BioRender.com.

• 

  FIGURE 3. Modulators of ANGPTL4. ANGPTL4 expression is regulated by various factors, including specific nutritional and metabolic states, transcription factors, certain activators and inhibitors, inflammatory molecules, drugs, and posttranslational modifications. Created with BioRender.com.

• 

  FIGURE 4. Role of ANGPTL4 in primary nephrotic syndrome. The specific regulatory mechanisms and intervention targets of podocytes and circulating ANGPTL4 in the pathogenesis of primary nephrotic syndrome are delineated. Podocyte-secreted ANGPTL4 modulates various cellular functions, including oxidative stress, apoptosis and cytoskeletal rearrangement. In contrast, circulating ANGPTL4 undergoes negative feedback regulation in response to substantial proteinuria. The intricate mechanistic actions of these ANGPTL4 entities are explained in the text. The arrows in the figure signify promoting effects, whereas the blocked arrows denote inhibitory effects. Created with BioRender.com.