Expression of epidermal growth factor in the developing rat kidney

2005 ◽  
Vol 288 (1) ◽  
pp. F227-F235 ◽  
Author(s):  
Ju-Young Jung ◽  
Ji-Hyun Song ◽  
Can Li ◽  
Chul-Woo Yang ◽  
Tae-Cheon Kang ◽  
...  

Epidermal growth factor (EGF) is important in mammalian renal development. In our study, we investigated the detailed distribution and the time of the first appearance of EGF in developing rat kidney. Kidneys from embryonic 18 ( E18)- and 20-day-old ( E20) fetuses, postnatal 1 ( P1)-, 3 ( P3)-, 7 ( P7)-, 14 ( P14)-, and 21-day-old ( P21) pups, and adults were processed for immunohistochemistry and electronmicroscopy. In adult rat kidney, EGF immunoreactivity was found in distal tubule including the thick ascending limb (TAL) and portion 1 of distal convoluted tubule (DCT1), whereas no EGF immunoreactivity was seen in portion 2 of distal convoluted tubule (DCT2) and connecting tubule. In developing kidney, EGF-positive cells first appeared at P3 and were localized in the middle portion of the differentiating TAL of the corticomedullary junction. By P7, the abundance of EGF expression had dramatically increased in the medullary TAL. Between P14 and P21, EGF immunoreactivity was found in the TAL and the DCT for the first time. However, EGF-positive and EGF-negative cells were in the TAL in developing rat kidney. EGF-positive cells did not differ from negative cells in the expression of sodium transport proteins or in the proliferation rate at P3 and P7. In the TAL, smooth-surfaced cells had strong EGF immunoreactivity, but no EGF immunoreactivity was seen in the rough-surfaced cells with well-developed microvilli. Our results suggest that the expression of EGF in developing kidney plays an important role in the regulation of growth and differentiation of the loop of Henle during kidney development and that this may act in the paracrine mode.

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 777-784 ◽  
Author(s):  
H.S. Coles ◽  
J.F. Burne ◽  
M.C. Raff

Although normal cell death is known to occur in many developing vertebrate organs, it has not been thought to play an important part in the development of the mammalian kidney. We show here that normal cell death is found in both the nephrogenic region and medullary papilla of the developing rat kidney and, in each of these areas, it follows a distinct developmental time course. As many as 3% of the cells in these areas have a typical apoptotic morphology and the dead cells seem to be cleared rapidly (within 1–2 hours) by phagocytosis by neighbouring parenchymal cells. These values are similar to those in vertebrate neural tissues where 50% or more of the cells die during normal development, suggesting that large-scale death is a normal feature of kidney development. We also show that in vivo treatment with epidermal growth factor inhibits cell death in the developing kidney, consistent with the possibility that the cells normally die because they lack sufficient survival factors. Our findings suggest that the extent of normal cell death in developing animals is still greatly underestimated and they raise the possibility that many of these cell deaths may reflect limiting amounts of survival factors.


1993 ◽  
Vol 139 (2) ◽  
pp. 227-234 ◽  
Author(s):  
P. E. Jørgensen ◽  
S. D. Hilchey ◽  
E. Nexø ◽  
S. S. Poulsen ◽  
C. P. Quilley

ABSTRACT Large amounts of epidermal growth factor (EGF) are excreted in urine and the majority of this urinary EGF appears to be of renal origin. EGF is synthesized in the kidneys as a membrane-bound 160 kDa precursor, in the thick ascending limb of Henle and in the early part of the distal convoluted tubule. Very little is known about how EGF is released from cell membranes into urine but proteolytic cleavage of the membrane-bound EGF precursor seems likely. The purpose of this study was to examine whether plasma constituents are necessary for urinary excretion of EGF. In the rat isolated kidney perfused at a pressure of 90 mmHg with a modified Krebs–Henseleit buffer containing oncotic agents, the quantity of EGF excreted into the ureteral effluent was 67% of the amount excreted by the rat kidney in vivo. The EGF excreted by the isolated kidney behaved like urinary EGF upon gel filtration. Administration of the proteinase inhibitor aprotinin reduced urinary EGF excretion from the rat isolated perfused kidney by approximately 50%. In conclusion, the rat isolated perfused kidney excreted significant amounts of urinary EGF without having access to plasma, and EGF excretion was reduced by aprotinin. This is further evidence suggesting an intrarenal source of urinary EGF and suggests that the EGF precursor in the rat kidney is processed by enzyme(s) of renal origin. Journal of Endocrinology (1993) 139, 227–234


Neonatology ◽  
2001 ◽  
Vol 79 (1) ◽  
pp. 46-53 ◽  
Author(s):  
Toshiya Okada ◽  
Asako Iwamoto ◽  
Ken Kusakabe ◽  
Masafumi Mukamoto ◽  
Yasuo Kiso ◽  
...  

2004 ◽  
Vol 24 (2) ◽  
pp. 212-220 ◽  
Author(s):  
Seung-Hun Lee ◽  
Ju-Young Jung ◽  
Ki-Hwan Han ◽  
Chul-Woo Yang ◽  
Kyu-Bok Choi ◽  
...  

2000 ◽  
Vol 19 (1) ◽  
pp. 47-59 ◽  
Author(s):  
Michael A. Haralson ◽  
Samuel J. DiMari ◽  
Richard L. Hoover ◽  
Raymond C. Harris

1990 ◽  
Vol 10 (4) ◽  
pp. 353-362 ◽  
Author(s):  
Nashrudeen Hack ◽  
Paula Clayman ◽  
Karl Skorecki

We have previously demonstrated phospholipase C (PLC) independent activation of phospholipase A2(PLA2) by epidermal growth factor (EGF) in glomerular mesangial cells in culture. In the current study using glass beads to permeabilize [3H]- or [14C]-arachidonate labelled mesangial cells we demonstrate that guanine nucleotides modulate the EGF-mediated stimulation of arachidonic acid release (75% inhibition with 100 μM GDPβS and 108% augmentation with 100 μM GTPγS). GTPγS alone stimulated both the release of free arachidonic acid and production of diacylglycerol (DAG), while EGF itself neither stimulated DAG nor augmented the DAG response to GTPγS. These findings suggest the intermediacy of a G-protein in PLC-independent stimulation of PLA2 by a growth factor, and provide a model system for determining the relationship between G-protein intermediacy and the intrinsic tyrosine kinase activity of the growth factor receptor.


1990 ◽  
Vol 68 (6) ◽  
pp. 733-736 ◽  
Author(s):  
Paul R. Goodyer ◽  
Sharon Langshur ◽  
Jehane Fata

In mammalian kidney, epidermal growth factor (EGF) is produced as a small internal domain of an abundant high molecular weight peptide associated with the luminal membrane of the thick ascending limb of Henle's loop and distal convoluted tubule. At present, there is no evidence to indicate a mitogenic function for the EGF-containing molecule in kidney; consideration of its molecular structure suggests the possibility of a membrane-associated physiologic role. In this study, we examine regulation of renal EGF synthesis during induction of vitamin D deficiency in mice. Despite evidence of marked hyperparathyroidism, urinary excretion of EGF was equivalent in control (2.54 ± 0.72 μg/mg creatinine) and vitamin D deficient (2.13 ± 0.97 μg/mg creatinine) animals. Similarly, EGF mRNA levels in kidney were comparable in the two groups. These data indicate that parathyroid hormone has no effect on renal EGF regulation, although it is known to stimulate calcium reabsorption in distal nephron segments.Key words: epidermal growth factor, vitamin D, calcium, kidney, parathyroid hormone.


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