Renal growth hormone--insulin-like growth factor-I system in acute renal failure.
The renal growth hormone--insulin-like growth factor-I system in acute ischemic renal failure. Recovery from acute tubular necrosis (ATN) is accelerated by IGF-I therapy. Furthermore, the local renal growth hormone-IGF-I system may participate in the natural repair. We examined the IGF-I system in rat kidneys subjected to 60 minute ischemia compared to sham operated controls. Two days after injury, growth hormone receptor mRNA and IGF-I mRNA levels fell approximately 9 to 33% of control values. This was associated with a reduction in kidney immunoreactive IGF-I levels. In contrast, IGF-I receptor mRNA abundance was unchanged. However, plasma membrane IGF-I receptor binding on day 2 and day 7 was near double the control values (P < 0.01). Scatchard analysis revealed a near twofold increase in receptor number. Since receptor mRNA levels were unchanged, this implies receptor protein up-regulation. In contrast to unchanged IGF-I receptor mRNA levels, the abundance of mRNA levels of insulin-like growth factor binding proteins (IGFBP) -2, -3, -4 and -5 fell approximately 14 to 62% of control levels day 2 after injury (P < 0.05), suggesting reduced IGFBP production. Thus, the renal response to ischemic ATN, namely, low IGFBP mRNA levels and high IGF-I receptor number, may function to increase IGF-I bioavailability and thereby enhance the reparative actions of local and circulating IGF-I in ischemic ATN.
Tsao
T
T
Department of Medicine, Stanford University, California, USA.
Wang
J
J
Fervenza
F C
FC
Vu
T H
TH
Jin
I H
IH
Hoffman
A R
AR
Rabkin
R
R
D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D013006:Growth Hormone / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics; D012079:Renal Circulation
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone