Polypeptide growth factors in metanephric growth and segmental nephron differentiation

Abstract

Although the developing nephron expresses receptors for various polypeptide growth factors, the specific roles of such factors in renal organogenesis are unknown. Therefore, the effects of epidermal growth factor (EGF) (8.2 x 10(-11) M-1.6 x 10(-8) M), multiplication stimulating activity (MSA) (6.6 x 10(-10) M-1.3 x 10(-8) M) and transforming growth factor beta (TGF-beta) (1 x 10(-12) M-1 x 10(-9) M) on organotypic renal growth and segmental nephron differentiation were studied in a serum-free hormone-supplemented, murine metanephric organ culture system. Following culture in control or growth-factor-supplemented medium, explant growth was assessed, and explant growth and differentiation were determined morphometrically in four defined neprhon segments which were identified morphologically or immunohistologically with segment-specific antibodies and/or lectins: glomeruli, proximal tubules, thick ascending limb-early distal tubules, and collecting tubules. Results showed that EGF increased overall renal growth and specific differentiation of distal elements, but retarded differentiation of glomeruli and proximal tubules. EGF also induced hyperplastic cystic malformation in proximal tubules. MSA stimulated explant growth and promoted segmental differentiation of all tubular segments. TGF-beta globally retarded in vitro nephrogenesis. Such data demonstrate that polypeptide growth factors have multiple and often disparate effects on overall renal growth in relation to differentiation of discrete nephron segments and provide insight into the factors which may regulate normal and abnormal renal embryogenesis.