Increased expression of ornithine decarboxylase in distal tubules of early diabetic rat kidneys: are polyamines paracrine hypertrophic factors?
Polyamines are small biogenic molecules that are essential for cell cycle entry and progression and proliferation. They can also contribute to hypertrophy. The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, increases in the early diabetic kidney to enable renal hypertrophy. Inhibition of ODC in early diabetes attenuates diabetic renal hypertrophy and glomerular hyperfiltration. The current studies examine the temporal profile of renal ODC protein expression and localization, intrarenal polyamine levels, and sites of proliferation in kidneys of rats during the first 7 days of streptozotocin diabetes. ODC mRNA and protein content were increased in diabetic kidneys. High-performance liquid chromatography analysis showed increased intrarenal polyamine concentrations peaking after 24 h of diabetes. A subsequent increase in the number of proliferating proximal tubular cells was detected by in vivo 5-bromodeoxyuridine (BrdU) incorporation on day 3. Surprisingly, immunohistochemical studies revealed that increased ODC protein was apparent only in distal nephrons, whereas the main site of diabetic kidney hypertrophy is the proximal tubule. These findings raise the possibility that polyamines produced in the distal nephron may mediate the early diabetic kidney growth of the proximal tubules via a paracrine mechanism.
Deng
Aihua
A
Department of Medicine, University of California and VA San Diego Health Care System, 3350 La Jolla Village Drive, San Diego, CA 92161-9151, USA.
Munger
Karen A
KA
Valdivielso
Jose M
JM
Satriano
Joseph
J
Lortie
Mark
M
Blantz
Roland C
RC
Thomson
Scott C
SC
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001973:Bromodeoxyuridine; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006984:Hypertrophy; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000201:enzymology / Q000473:pathology; D007686:Kidney Tubules, Distal / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011073:Polyamines / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000728:Androgens; D011073:Polyamines; D009955:Ornithine Decarboxylase; D001973:Bromodeoxyuridine