An endothelial growth factor involved in rat renal development

Area of Science:

• Developmental Biology
• Cell Biology
• Renal Physiology

Background:

• The developing kidney involves intricate interactions between epithelial and endothelial cells.
• Reciprocal signaling pathways likely regulate renal ontogeny.

Purpose of the Study:

• To investigate if metanephrogenic mesenchymal cells secrete factors that stimulate endothelial cell growth.
• To identify and characterize such mitogenic factors during kidney development.

Main Methods:

• Endothelial mitogenic assays and sequential chromatography were used to isolate proteins from conditioned media of rat metanephrogenic mesenchymal cells (7.1.1 cell line).
• Amino acid analysis identified the isolated protein as hepatoma-derived growth factor (HDGF).
• HDGF's role was confirmed using Cos-7 cells transfected with HDGF cDNA, and its expression pattern was analyzed via immunoaffinity purified antipeptide antibodies and in situ hybridization with digoxigenin-labeled riboprobes.

Main Results:

• HDGF was identified as an endothelial mitogen secreted by metanephrogenic mesenchymal cells.
• HDGF stimulated endothelial DNA synthesis.
• HDGF was widely distributed in the early embryonic kidney, concentrating at sites of active morphogenesis, and its expression decreased in adult kidneys, with transcripts mainly found in distal tubules.
• In situ hybridization revealed HDGF mRNA abundance during kidney development, particularly at sites of nephron morphogenesis and in ureteric bud cells, diminishing in adult kidneys.

Conclusions:

• HDGF is an endothelial mitogen crucial for kidney development.
• HDGF expression is temporally and spatially regulated during renal ontogeny, correlating with nephrogenesis.
• The findings highlight HDGF's role in the reciprocal signaling between mesenchymal and endothelial cells during kidney formation.