Renal tubular cells are potential targets for epidermal growth factor

Abstract

Epidermal growth factor (EGF) is a potent polypeptide mitogen with various receptor-mediated growth effects on cells from the skin, breast, and gastrointestinal tract. Recent studies indicate that EGF is produced in the kidney and is excreted in the urine, but the biological significance of renal EGF is uncertain. We demonstrate in vitro mitogenicity of EGF for LLC-PK1 cells, a tubular epithelial cell line derived from pig kidney cortex. Furthermore, when subconfluent monolayers of LLC-PK1 cells are exposed to EGF for 24 h, sodium-dependent phosphate transport is stimulated (209-410% of control). These cells possess EGF-specific high-affinity binding sites at their surface (Kd 300-700 pM) but cannot synthesize the growth factor. EGF binding sites are not a peculiarity of the LLC-PK1 cell line, since similar sites are present on MDCK cells (derived from dog kidney distal tubule or collecting duct), primary cultures of mouse proximal tubular cells, and freshly prepared membrane fractions from mouse kidney. Cortical basolateral membranes are highly enriched in EGF binding sites, whereas EGF binding by brush-border membrane fractions is minimal and is compatible with contamination.

PKD2 Functions as an Epidermal Growth Factor-Activated Plasma Membrane Channel

“…Thus, we proceeded with functional studies using the LLC-PK 1 PKD2 cells. Previous work had demonstrated that LLC-PK 1 cells express endogenous PKD2 and functional EGFR (16,19,25,28,42). Initial single channel recordings in cell-attached patches of LLC-PK 1 PKD2 cells indicated the existence of an EGF-activated channel with a conductance in K ϩ higher than that in Na ϩ or in Ca 2ϩ (see the supplemental material).…”

Effect of Epidermal Growth Factor on Sodium–Dependent <i>L</i>–Alanine Transport in LLC–PK1 Cells

“…Furthermore, Amsler et al [21]reported that LLC–PK1 cells regulate the rate of sodium–dependent amino acid transport during growth. Goodyer et al [12]also reported that the sodium–dependent phosphate uptake in LLC–PK1 cells was stimulated by EGF only in subconfluent cells. These authors suggested that the disappearance of the effect on phosphate uptake is related to the effect of cell–cell contacts on the EGF response.…”

“…On the other hand, the LLC–PK1 cell line expresses different types of G–protein–coupled receptor systems [10, 11]and demonstrates a proliferative response to the protein tyrosine kinase stimulating growth factor, EGF [12]. It has also been reported that 12– o –tetradecanoylphorbol–13–acetate (TPA) stimulates sodium–coupled phosphate and amino acid transport in LLC–PK1 cells via activation of protein kinase C [13, 14].…”

Depressed Urinary Excretion of Epidermal Growth Factor in Psoriasis

“…Though there is some experimental evidence for glomerular action of renal EGF in the rat [25], the best-documented function of EGF is to maintain distal nephron integrity and func tion [8][9][10]. In addition, it may regulate renal hemody namics, as suggested by the finding that urinary EGF excretion correlates directly with renal blood flow in women affected by arterial hypertension (r = 0.73, n = 13. p < 0.01) [personal unpubl.…”

“…A specific messenger RNA for the EGF precursor is present in the kidney at the level of thick ascending limb of Henle's loop, and early distal convoluted tubule [4], Synthesis of EGF by the kidney suggests the possibil ity of a local biological function. Similar to the protec tive and repairing effect exerted by EGF in the gastroin testinal apparatus [7], the action of renal EGF may serve as a trophic function for the distal urinary epithelium and promote renal cell mitogenic response after loss of nephron [8]. In addition, the findings that EGF affects sodium absorption in isolated perfused segments of rab bit cortical collecting tubules [9.…”