Biochemistry

Kidney International (1992) 41, 768–777; doi:10.1038/ki.1992.120

Early increased renal procollagen alpha1(IV) mRNA levels in streptozotocin induced diabetes

Chun-Gyoo Ihm, Grace S L Lee, Cynthia C Nast, Alexander Artishevsky, Roy Guillermo, Patricia S Levin, Richard J Glassock and Sharon G Adler

Departments of Medicine and Pathology, Harbor-UCLA Medical Center, Torrance, and the UCLA School of Medicine, Los Angeles, California, USA

Correspondence: Sharon Adler MD, Harbor-UCLA Medical Center, Division of Nephrology, 1000 W. Carson St., Torrance, California 90509, USA.

Received 14 June 1991; Revised 13 August 1991; Accepted 19 August 1991.

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Abstract

Early increased renal procollagen alpha1(IV) mRNA levels in streptozotocin induced diabetes. Changes in renal procollagen mRNA levels were measured shortly after the induction of streptozotocin induced diabetes in the rat. "Medullary" procollagen alpha1(IV) levels seven days after diabetes induction was significantly higher in untreated diabetic rats (DM, N = 12; 244 plusminus 57% of the mean control value), than in diabetic rats receiving small doses of insulin insufficient to achieve euglycemia (NPH, N = 10; 87 plusminus 12%) and in diluent injected nondiabetic control rats (C, N = 15; 100 plusminus 12% P < 0.01, DM vs. C and DM vs. NPH). "Medullary" procollagen alpha1(I) mRNA levels were numerically increased in DM to a lesser degree (141 plusminus 5%, ANOVA not significant) compared to C (100 plusminus 13%), and this small increment was further normalized by insulin treatment (NPH, 120 plusminus 11%). A trend for increased beta-actin mRNA levels in DM did not reach significance (P > 0.05). Increases in "medullary" procollagen mRNA levels did not correlate with kidney weight, glomerular tuft volume, creatinine clearance, food intake, or body weight gain, and occurred when renal morphology was normal by light microscopy. Statistically significant but weak correlations were noted between the serum glucose levels and "medullary" procollagen alpha1(IV) mRNA levels (r = 0.43, P < 0.05). In addition, weak correlations were noted between glycosuria and "medullary" procollagen alpha1(I) levels (r = 0.38, P < 0.05). In situ hybridization studies localized the increased procollagen alpha1(IV) mRNA levels predominantly in the DM group primarily in the deep cortex and medullary outer stripe of proximal tubules. Glomerular procollagen alpha1(IV), alpha1(I), alpha1(III) and beta-actin mRNA levels were not increased in untreated diabetic rats 7 or 28 days after diabetes induction. Thus, tubular procollagen alpha1(IV) mRNA levels increased prior to any measurable change in glomerular levels and were ameliorated by insulin administration.

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References

  1. Hostetter TH, Troy JL, Brenner BM: Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int 19:410–415, 1981 | PubMed | ISI | ChemPort |
  2. Zatz R, Meyer TW, Rennke HG, Brenner BM: Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc Natl Acad Sci USA 82:5963–5967, 1985 | Article | PubMed | ChemPort |
  3. Michels LD, O 'Donnell MP, Keane WF: Glomerular hemodynamic and structural correlations in long-term diabetic rats. J Lab Clin Med 103:840–847, 1984
  4. Zatz R, Dunn BR, Meyer TW, Anderson S, Rennke HG, Brenner BM: Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 77:1925–1930, 1986 | PubMed | ISI | ChemPort |
  5. O'Donnell MP, Kasiske BL, Keane WF: Glomerular hemodynamic and structural alterations in experimental diabetes mellitus. FASEB J 2:2339–2347, 1988 | PubMed | ChemPort |
  6. Scholey JW, Meyer TW: Control of glomerular hypertension by insulin administration in diabetic rats. J Clin Invest 83:1384–1389, 1989 | PubMed | ISI | ChemPort |
  7. Seyer-Hansen K: Renal hypertrophy in experimental diabetes mellitus. Kidney Int 23:643–646, 1983 | PubMed | ChemPort |
  8. Rasch R, Rytter Nörgaard JO: Renal enlargement: Comparative autoradiographic studies of 3H-thymidine uptake in diabetic and uninephrectomized rats. Diabetologia 25:280–287, 1983 | Article | PubMed | ISI | ChemPort |
  9. Steffes MW, Brown DM, Basgen JM, Mauer SM: Amelioration of mesangial volume and surface alterations following islet transplantation in diabetic rats. Diabetes 29:509–515, 1980 | PubMed | ISI | ChemPort |
  10. Osterby R, Gunderson HJG: Fast accumulation of basement membrane material and the rate of morphological changes in acute experimental diabetic glomerular hypertrophy. Diabetologia 18:493–500, 1980 | PubMed | ISI | ChemPort |
  11. Steffes MW, Brown DM, Mauer SM: Diabetic glomerulopathy following unilateral nephrectomy in the rat. Diabetes 27:35–41, 1977
  12. Armanni L: Der Diabetes Mellitus, Vierzehnte Vorlesung, edited by Cantani A, Denickes Verlag, Berlin, 1877, pp. 315–332
  13. Ebstein W: Deutsch Arch Klin Med 30:143–185, 1881
  14. Seyer-Hansen K, Hansen J, Gunderson HJG: Renal hypertrophy in experimental diabetes. A morphometric study. Diabetologia 18:501–505, 1980 | PubMed | ChemPort |
  15. Rasch R: Tubular lesions in streptozotocin diabetic rats. Diabetologia 27:32–37, 1984 | PubMed | ISI | ChemPort |
  16. Kumar AM, Gupta RK, Spitzer A: Intracellular sodium in proximal tubules of diabetic rats. Role of glucose. Kidney Int 33:792–797, 1988 | PubMed | ChemPort |
  17. Weinman EJ, Suki WN, Eknoyan G: D-glucose enhancement of water reabsorption in proximal tubule of the rat kidney. Am J Physiol 231:777–780, 1976
  18. Khadouri C, Barlet-Bas C, Doucet A: Mechanism of increased tubular Na-K-ATPase during streptozotocin-induced diabetes. Pflügers Arch 409:296–301, 1987
  19. Abrass CK: Diabetic proteinuria. Glomerular or tubular origin? Am J Nephrol 4:337–346, 1984
  20. Ritchie S, Waugh D: The pathology of Armanni-Ebstein diabetic nephropathy. Am J Pathol 33:1035–1043, 1957
  21. Tisher CC, Hostetter TH: Diabetic Nephropathy, in Renal Pathology with Clinical and Functional Correlations, edited by Tisher CC, Brenner BM, Philadelphia, JP Lippincott Co., pp. 1309–1334
  22. Bader R, Bader H, Grund KE, Markensen-Haen S, Christ H, Bohle A: Structure and function of the kidney in diabetic glomerulosclerosis: Correlations between morphologic and functional parameters. Pathol Res Pract 167:204–216, 1980 | PubMed | ISI | ChemPort |
  23. Abrass CK, Peterson CV, Raugi GJ: Phenotypic expression of collagen types in mesangial matrix of diabetic and nondiabetic rats. Diabetes 37:1695–1702, 1988 | PubMed | ISI | ChemPort |
  24. Brownlee M, Spiro RG: Glomerular basement membrane metabolism in the diabetic rat. In vivo studies. Diabetes 28:121–125, 1979
  25. Cohen MP, Vogt C: Collagen synthesis and secretion by isolated rat renal glomeruli. Biochim Biophys Acta 393:78–87, 1975 | PubMed |
  26. Romen H, Heck T, Rauscher G, Lange HV, Hempel K: The glomerular basement membrane. First International Symposium. Renal Physiol 3:324–329, 1980
  27. Hasslacher C, Reichenbacher R, Gechter F, Timpl R: Glomerular basement membrane synthesis and serum concentration of type IV collagen in streptozotocin-diabetic rats. Diabetologia 26:150–157, 1984
  28. Cohen MP, Khalifa A: Renal glomerular collagen synthesis in streptozotocin diabetes. Reversal of increased basement membrane synthesis with insulin therapy. Biochim Biophys Acta 500:395–404, 1977 | PubMed | ISI | ChemPort |
  29. Kefalides NA: Basement membrane research in diabetes mellitus. Collagen Relat Res 1:295–299, 1981
  30. Hasslacher CH, Wall P: Influence of diabetes control on synthesis of protein and basement membrane collagen in isolated glomeruli of diabetic rats. Res Exp Med (Berl) 176:247–253, 1980
  31. Pfeffer JM, Pfeffer MA, Frohlich ED: Validity of an indirect tail cuff method for determining systolic arterial blood pressure in unanesthetized normotensive and spontaneously hypertensive rats. J Lab Clin Med 78:957–962, 1971 | PubMed | ISI | ChemPort |
  32. vanDamme B, Koudstaal J: Measuring glomerular diameters in tissue sections. Yirchow Arch 369:283–291, 1976
  33. Bilous RW, Mauer JM, Basgen JM, Steffes MW: Estimation of mean glomerular volume in patients with insulin-dependent diabetes mellitus. Kidney Int 32:930–932, 1987 | PubMed | ChemPort |
  34. Hirose K, Osterby R, Nozawa M, Gundersen HJG: Development of glomerular lesions in experimental long-term diabetes in the rat. Kidney Int 21:689–695, 1982 | PubMed | ISI | ChemPort |
  35. Maniatis T, Fritsch EF, Sambrook J: Molecular Cloning—A Laboratory Manual. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory Publications, 1982
  36. Chomczynski P, Sacchi N: Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-guanidinium chloroform extraction. Anal Biochem 162:156–159, 1987 | Article | PubMed | ISI | ChemPort |
  37. Spiro R: Studies on the renal glomerular basement membrane. Preparations and chemical composition. J Biol Chem 242:1915–1922, 1967 | PubMed | ISI | ChemPort |
  38. Kurkinen M, Condon MR, Blumberg B, Barlow DP, Quinones S, Saus J, Pihlajaniemi T: Extensive homology between the carboxyl-terminal peptides of mouse alpha 1(IV) and alpha 2(IV) collagen. J Biol Chem 262:8496–8499, 1987 | PubMed | ISI | ChemPort |
  39. Chu ML, Myers JC, Bernard MP, Ding J-F, Ramirez F: Cloning and characterization of five overlapping cDNAs specific for the human pro alpha 1(I) collagen chain. Nucleic Acid Res 10:5925–5934, 1982 | PubMed | ISI | ChemPort |
  40. Chu M-L, Weil D, De Wet W, Bernard M, Sippola M, Ramirez F: Isolation of cDNA and genomic clones encoding human proalpha 1(III) collagen. Partial characterization of the 3' end region of the gene. J Biol Chem 260:4357–4363, 1985 | PubMed | ISI | ChemPort |
  41. Nudel V, Zakut R, Shani M, Neuman S, Levy Z, Yaffe D: The nucleotide sequence of the rat cytoplasmic beta-actin gene. Nucleic Acids Res 11:1759–1177, 1983 | PubMed | ISI | ChemPort |
  42. Nast CC, Adler SG, Artishevsky A, Kresser CT, Ahmed K, Anderson PS: Cyclosporine induces elevated procollagen alpha1(I) mRNA levels in the rat renal cortex. Kidney Int 39:631–638, 1991 | PubMed |
  43. Salido EC, Yen PH, Shapiro LJ, Fisher DA, Barajas L: In situ hybridization of prepro-epidermal growth factor mRNA in the mouse kidney. Am J Physiol (Renal Fluid Electrol Physiol 25) 256:F632–F638, 1989 | PubMed | ISI | ChemPort |
  44. Ledbetter S, Copeland EJ, Noonan D, Vogeli G, Hassell JR: Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. Diabetes 39:196–203, 1990 | PubMed | ISI | ChemPort |
  45. Killen PD, Ebihara I, Martin GR, Ortola F, Brenner BM: mRNA levels for laminin and collagen IV chains are elevated in diabetic kidneys. (abstract) Kidney Int 31:171, 1987
  46. Poulsom R, Kurkinen M, Prockop DJ, Boot-Hanford RP: Increased steady-state levels of laminin Bl mRNA in kidneys of long-term streptozotocin-diabetic rats. No effect of an aldose reductase inhibitor. J Biol Chem 263:10072–10076, 1988 | PubMed | ISI | ChemPort |
  47. Ziyadeh FN, Snipes ER, Watanabe M, Alvarez RJ, Goldfarb S, Haverty TP: High glucose induces cell hypertrophy and stimulates collagen gene transcription in proximal tubule. Am J Physiol 259 (Renal Fluid Electrol Physiol 28):F704–F714, 1990 | PubMed | ISI | ChemPort |
  48. Ayo SH, Radnick RA, Garoni JA, Glass WF II, Kreisberg JI: High glucose causes an increase in extracellular matrix proteins in cultured mesangial cells. Am J Pathol 136:1339–1348, 1990 | PubMed | ISI | ChemPort |
  49. Cagliero E, Maiello M, Boeri D, Roy S, Lorenzi J: Increased expression of basement membrane component in human endothelial cells cultured in high glucose. J Clin Invest 82:735–738, 1988 | PubMed | ISI | ChemPort |
  50. Muona P, Peltonen J, Jaakkola S, Uitto J: Increased matrix gene expression by glucose in rat neural connective tissue cells in culture. Diabetes 40:605–611, 1991
  51. Arison RN, Ciaccio EI, Glitzer MS, Cassaro JA, Pruss MP: Light and electron microscopy of lesions in rats rendered diabetic with streptozotocin. Diabetes 16:51–56, 1967 | PubMed | ISI | ChemPort |
  52. Evan AP, Mong SA, Gattone VH, Connors BA, Aronoff GR, Luft FC: The effect of streptozotocin and streptozotocin-induced diabetes on the kidney. Renal Physiol (Basel) 7:78–89, 1984
  53. Viberti C, Mackintosh D, Keen H: Determinants of the penetration of proteins through the glomerular barrier in insulin-dependent diabetes mellitus. Diabetes 32:92–95, 1983
  54. Ledbetter SR, Wagner CW, Martin GR, Rohrbach DH, Hassell JR: Response of diabetic basement membrane-producing cells to glucose and insulin. Diabetes 36:1029–1034, 1987
  55. Snipes ER, Haverty TP, Goldfarb S, Ziyadeh FM: Glucose-induced and secretion of collagen type IV and I in mouse proximal tubule cells in culture: Modulation by insulin. (abstract) Clin Res 37:502A, 1989
  56. Cohen MP, Khalifa A: Renal glomerular collagen synthesis in streptozotocin diabetes. Reversal of increased basement membrane synthesis with insulin therapy. Biochim Biophys Acta 500:395–404, 1977 | PubMed | ISI | ChemPort |
  57. Cortes P, Dumler F, Venkatachalam KK, Goldman J, Sastry KS, Venkatachalam H, Bernstein J, Levin NW: Alterations in glomerular RNA in diabetic rats: Roles of glucagon and insulin. Kidney Int 20:491–499, 1981

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