Focal expression of insulin-like growth factor I in rat kidney collecting duct.

To address the question of insulin-like growth factor (IGF) I localization and synthesis in kidney, we used two complementary experimental approaches: immunohistochemistry of fixed paraffin-embedded rat kidney sections; and measurement of IGF I mRNA in isolated components of the rat nephron, using a highly sensitive and specific solution hybridization assay. Immunostainable IGF I was localized exclusively to principal cells of cortical and medullary collecting ducts. Administration of growth hormone to hypophysectomized rats for 8 d resulted in enhanced immunohistochemical staining of IGF I within collecting ducts, but no detectable IGF I in other portions of the nephron. The abundance of IGF I mRNA was 7-12-fold higher in isolated papillary collecting ducts than in proximal tubules or glomeruli, and was enriched 10-fold compared with whole kidney. Our data demonstrate colocalization of IGF I and IGF I mRNA in the collecting duct, consistent with focal expression of the IGF I gene at this site.

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Expression of the genes encoding the rat renal insulin-like growth factor-I system.

Journal of the American Society of Nephrology ◽

10.1681/asn.v651511 ◽

1995 ◽

Vol 6 (5) ◽

pp. 1511-1518

Author(s):

R Rabkin ◽

M Brody ◽

L H Lu ◽

C Chan ◽

A M Shaheen ◽

...

Keyword(s):

Growth Factor ◽

Rat Kidney ◽

Thick Ascending Limb ◽

Insulin Like Growth Factor ◽

Igf Binding Proteins ◽

Factor I ◽

Collecting Ducts ◽

Igf I ◽

Growth Factor I ◽

Convoluted Tubules

Insulin-like growth factor-I (IGF-I) modulates renal function, growth, and repair. IGF-I produced in the kidney is one component of the intrarenal IGF-I system comprising the IGF-I receptor (IGF-IR) and six IGF-binding proteins (IGFBP). Because of the physiologic importance of IGF-I and its potential therapeutic properties, the renal sites of mRNA synthesis for IGF-I, IGF-IR, and IGFBP-I through IGFBP-5 were characterized in rat kidney by in situ hybridization. Anatomical heterogeneity was prominent. IGF-I mRNA was present in the thick ascending limb of Henle in the outer medulla, whereas IGF-IR mRNA was diffusely present at low levels throughout the kidney. IGFBP-I mRNA was localized to cells within the distal convoluted tubules as well as the thick ascending limb of Henle. IGFBP-2 mRNA was expressed in glomeruli, medullary ray collecting ducts, pelvic smooth muscle and uroepithelium, and the papilla tip; IGFBP-3 mRNA was localized to the cortical interstitium, whereas IGFBP-4 mRNA was expressed in proximal tubules, medullary ray collecting ducts, and glomeruli. IGFBP-5 was strongly positive throughout the medulla with lesser expression in the distal convoluted tubules and glomeruli. This study highlights the complexity of the intrarenal IGF-I system. The striking heterogeneity of IGFBP gene expression suggests that the various IGFBP may have diverse modulatory effects on the action of IGF-I or discrete effects of their own.

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Expression of the insulin-like growth factor system in the hypokalemic rat kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1997.272.5.f661 ◽

1997 ◽

Vol 272 (5) ◽

pp. F661-F667 ◽

Cited By ~ 3

Author(s):

R. M. Rohan ◽

T. G. Unterman ◽

L. Liu ◽

M. K. Hise

Keyword(s):

Growth Factor ◽

Binding Protein ◽

Collecting Duct ◽

Rat Kidney ◽

Insulin Like Growth Factor ◽

Distal Nephron ◽

Igf System ◽

Igf I ◽

Igf Binding ◽

Igf Binding Protein

We studied the renal expression of the insulin-like growth factor (IGF) system to gain a better perspective of its potential role in the hyperplastic adaptation of the distal nephron to potassium deficiency. Rats were pair fed 1% or 0.002% potassium diets for periods up to 10 days. IGF-I mRNA was diminished in potassium-deficient rats within 4 days, whereas mRNA for IGF binding protein-1 (IGFBP-1), a collecting duct-associated protein, was increased by day 7. At day 10 mRNA for IGFBP-1 in potassium-deficient animals averaged 2.07 +/- 0.53 (mean +/- SD, relative densitometry units) compared with 0.89 +/- 0.26 in control rats (n = 4, P = 0.002). Conversely, IGFBP-3, a binding protein whose mRNA has been localized to the interstitial compartment, averaged 2.40 +/- 0.02 in potassium-deficient rats and 4.77 +/- 0.05 in controls (n = 4, P < 0.03) at day 10 of treatment. Immunohistochemistry performed using a specific IGFBP-1 antibody revealed hyperplasia of distal nephron segments along with an increase in IGFBP-1 in potassium-depleted rats. These data suggest that IGFBP-1 may play an important role in the control of cellular adaptations in the hypokalemic rat kidney either directly by influencing cell migration or indirectly by localizing IGF-I to the distal nephron.

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Dual regulation of insulin-like growth factor I expression during renal hypertrophy

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.2.f252 ◽

1989 ◽

Vol 257 (2) ◽

pp. F252-F261 ◽

Cited By ~ 1

Author(s):

R. Lajara ◽

P. Rotwein ◽

J. D. Bortz ◽

V. A. Hansen ◽

J. L. Sadow ◽

...

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Compensatory Hypertrophy ◽

Insulin Like Growth Factor ◽

Renal Hypertrophy ◽

Factor I ◽

Collecting Ducts ◽

Igf I ◽

Hypophysectomized Rats ◽

Growth Factor I

We examined the regulation of insulin-like growth factor I (IGF-I) in kidney during the renal hypertrophy produced by two different experimental models: growth hormone treatment of hypophysectomized rats and compensatory hypertrophy subsequent to unilateral nephrectomy. Immunostaining for IGF-I in collecting ducts was enhanced in kidneys from growth hormone-repleted hypophysectomized rats, and the levels of IGF-I mRNAs were increased. In compensatory hypertrophy, no enhancement of the intensity of immunostaining was observed in kidneys of nephrectomized rats until 5 days postnephrectomy, at which time immunostainable IGF-I was increased markedly in medullary collecting ducts of hypertrophied kidneys compared with kidneys from sham-operated animals. No difference in steady-state levels of any IGF-I mRNA species was detected in whole kidneys or in collecting ducts from nephrectomized or sham-operated rats at any time postnephrectomy. Our findings demonstrate an increase in both IGF-I mRNA and in immunostainable IGF-I in collecting duct in the setting of growth hormone-induced renal hypertrophy but suggest that other, possibly translational, mechanisms underlie the induction of IGF-I synthesis during compensatory hypertrophy.

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Recombinant human insulin-like growth factor: testing the somatomedin hypothesis in hypophysectomized rats

Journal of Endocrinology ◽

10.1677/joe.0.1120123 ◽

1987 ◽

Vol 112 (1) ◽

pp. 123-132 ◽

Cited By ~ 83

Author(s):

A. Skottner ◽

R. G. Clark ◽

I. C. A. F. Robinson ◽

L. Fryklund

Keyword(s):

Growth Factor ◽

Bone Growth ◽

Body Weight Gain ◽

Insulin Like Growth Factor ◽

Recombinant Human Insulin ◽

Poor Growth ◽

Igf I ◽

Hypophysectomized Rats ◽

Growth Promoting

ABSTRACT The in-vivo biological activity of recombinant methionyl insulin-like growth factor I (met-IGF-I) was demonstrated in hypophysectomized rats by following blood glucose after an i.v. bolus injection of met-IGF-I; a dose-dependent decrease in blood sugar was seen. Membrane transport was studied using the non-metabolizable amino acid α-aminoisobutyric acid; stimulation was obtained with the highest dose used (90 μg/rat). To test the original somatomedin hypothesis, growth studies were performed in hypophysectomized rats. Two or three doses of met-IGF-I were given with three different administration regimes (i.v. or s.c. infusion, or s.c. injections twice daily) for 6 or 8 days. Little growth-promoting activity was observed, with a significant effect on body weight gain obtained only when met-IGF-I was given continuously at the highest dose used (180 μg/day). No effect was seen on the in-vivo uptake of radioactive sulphate into cartilage. Epiphyseal cartilage width increased slightly at the highest dose of met-IGF-I, but only when the hormone was given by infusion. When 180 μg met-IGF-I/day were given by injections, a significant effect on longitudinal bone growth was obtained (90 μm above control). The levels of IGF in the serum were not measurably increased after s.c. administration of met-IGF-I, whereas after i.v. infusion, significantly raised levels were obtained at the higher dose rates (3·0 ± 0·3 and 2·8 ± 0·1 units/ml). Growth hormone was much more effective than met-IGF-I even at 50-fold lower doses. Priming the animals with 10 mu. bovine GH/day followed by combined infusions of GH and met-IGF-I did not reveal any potentiating effects of met-IGF-I in the presence of GH. We conclude that met-IGF-I is a relatively poor growth-promoting agent when given systemically, and that somatomedins are more likely to act as local growth factors rather than as circulating mediators of the growth-promoting effects of GH. J. Endocr. (1987) 112, 123–132

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Colocalization of insulin-like growth factor-binding protein with insulin-like growth factor I

AJP Renal Physiology ◽

10.1152/ajprenal.1991.261.1.f22 ◽

1991 ◽

Vol 261 (1) ◽

pp. F22-F28 ◽

Cited By ~ 3

Author(s):

S. Kobayashi ◽

D. R. Clemmons ◽

M. A. Venkatachalam

Keyword(s):

Growth Factor ◽

Cultured Cells ◽

Binding Protein ◽

Insulin Like Growth Factor ◽

Intense Staining ◽

Factor Binding ◽

Factor I ◽

Collecting Ducts ◽

Igf I ◽

Growth Factor I

We report the localization of insulin-like growth factor I (IGF-I) and a 25-kDa form of insulin-like growth factor-binding protein (IGF-BP-1) in adult rat kidney. The antigens were localized using a rabbit anti-human IGF-I antibody, and a rabbit anti-human IGF-BP-1 antibody raised against human 25-kDa IGF-BP-1 purified from amniotic fluid. Immunohistochemistry by the avidin-biotin peroxidase conjugate technique showed that both peptides are located in the same nephron segments, in the same cell types. The most intense staining was in papillary collecting ducts. There was moderate staining also in cortical collecting ducts and medullary thick ascending limbs of Henle's loop. In collecting ducts the antigens were shown to be present in principal cells but not in intercalated cells. In distal convoluted tubules, cortical thick ascending limbs, and in structures presumptively identified as thin limbs of Henle's loops there was only modest staining. The macula densa, however, lacked immunoreactivity. Colocalization of IGF-I and IGF-BP-1 in the same cells supports the notion, derived from studies on cultured cells, that the actions of IGF-I may be modified by IGF-BPs that are present in the same location.

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