Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1979 Aug 15;182(2):337–345. doi: 10.1042/bj1820337

Biosynthesis of skin collagens in normal and diabetic mice.

P Kern, M Moczar, L Robert
PMCID: PMC1161312  PMID: 508288

Abstract

Synthesis of collagens in vitro was studied on minced mouse skins incubated with [3H]-proline in organ-culture conditions. A comparative study was carried out on genetically diabetic mice (KK strain) and control mice (Swiss strain). After incubation, neutral-salt-soluble and acid-soluble collagens were extracted. The insoluble dermis was digested by pepsin and type I and type III collagens separated by differential precipitation in neutral salt solutions. Type I and Type III collagens were characterized by ion-exchange and molecular-sieve chromatography, amino acid analysis and by the characterization of CNBr peptides. In diabetic-mouse skin, the relative proportion of type III collagen was significantly higher than in control-mouse skin. The incorporation of radioactively labelled proline into hydroxyproline of type III collagen was significantly faster in diabetic-mouse skin than in control-mouse skin.No significant modifications in the total collagen content of the skin or of their rates of synthesis were observed between the two strains. Alteration in the ratio of type III to type I collagen in the diabetic-mouse skin can be interpreted as a sign of alteration of the regulation of collagen biosynthesis and may be related to the structural alterations observed in the diabetic intercellular matrix.

Full text

PDF
340

Images in this article

341Fig. 3.
on p.341

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anesey J., Scott P. G., Veis A., Chyatte D. The isolation of a soluble type III collagen precursor from rat skin. Biochem Biophys Res Commun. 1975 Feb 17;62(4):946–952. doi: 10.1016/0006-291x(75)90414-3. [DOI] [PubMed] [Google Scholar]
  2. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bailey A. J., Sims T. J., Le Lous, bazin S. Collagen polymorphism in experimental granulation tissue. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1160–1165. doi: 10.1016/0006-291x(75)90480-5. [DOI] [PubMed] [Google Scholar]
  4. Barnes M. J., Morton L. F., Bennett R. C., Bailey A. J., Sims T. J. Presence of type III collagen in guinea-pig dermal scar. Biochem J. 1976 Jul 1;157(1):263–266. doi: 10.1042/bj1570263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beisswenger P. J. Glomerular basement membrane: biosynthesis and chemical composition in the streptozotocin diabetic rat. J Clin Invest. 1976 Oct;58(4):844–852. doi: 10.1172/JCI108537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berenson G. S., Radhakrishnamurthy, Dalferes E. R., Jr, Ruiz H., Srinivasan S. R., Plavidal F., Brickman F. Connective tissue macromolecular changes in rats with experimentally induced diabetes and hyperinsulinism. Diabetes. 1972 Jun;21(6):733–743. doi: 10.2337/diab.21.6.733. [DOI] [PubMed] [Google Scholar]
  7. Byers P. H., McKenney K. H., Lichtenstein J. R., Martin G. R. Preparation of type III procollagen and collagen from rat skin. Biochemistry. 1974 Dec 3;13(25):5243–5248. doi: 10.1021/bi00722a030. [DOI] [PubMed] [Google Scholar]
  8. Chung E., Miller E. J. Collagen polymorphism: characterization of molecules with the chain composition (alpha 1 (3)03 in human tissues. Science. 1974 Mar;183(130):1200–1201. doi: 10.1126/science.183.4130.1200. [DOI] [PubMed] [Google Scholar]
  9. Craig R. D. Collagen biosynthesis in normal human skin, normal and hypertrophic scar and keloid. Eur J Clin Invest. 1975 Feb;5(1):69–74. doi: 10.1111/j.1365-2362.1975.tb00430.x. [DOI] [PubMed] [Google Scholar]
  10. Duhalult J., Lebon F., Boulanger M., Regnault F., Kern F. Microangiopathie diabetique: etude comparative chez l'homme et l'animal. Biorheology. 1974 Jun;11(3):167–178. [PubMed] [Google Scholar]
  11. Ehrenreich T., Susuki Y., Churg J., Oppermann W., Camerini-Dávalos R. A. Ultrastructure of glomerular lesions in KK mice. Adv Metab Disord. 1973;2(Suppl):271–280. doi: 10.1016/b978-0-12-027362-1.50034-0. [DOI] [PubMed] [Google Scholar]
  12. Epstein E. H., Jr (Alpha1(3))3 human skin collagen. Release by pepsin digestion and preponderance in fetal life. J Biol Chem. 1974 May 25;249(10):3225–3231. [PubMed] [Google Scholar]
  13. Francis M. J., Ellis J. P., Hockaday T. D. Skin collagen in diabetes mellitus in relation to treatment. Proc R Soc Med. 1974 Jan;67(1):35–36. [PMC free article] [PubMed] [Google Scholar]
  14. Fujii T., Kühn K. Isolation and characterization of pepsin-treated type III collagen from calf skin. Hoppe Seylers Z Physiol Chem. 1975 Nov;356(11):1793–1801. doi: 10.1515/bchm2.1975.356.2.1793. [DOI] [PubMed] [Google Scholar]
  15. Furthmayr H., Timpl R. Characterization of collagen peptides by sodium dodecylsulfate-polyacrylamide electrophoresis. Anal Biochem. 1971 Jun;41(2):510–516. doi: 10.1016/0003-2697(71)90173-4. [DOI] [PubMed] [Google Scholar]
  16. Goldstein S., Littlefield J. W., Soeldner J. S. Diabetes mellitus and aging: diminished planting efficiency of cultured human fibroblasts. Proc Natl Acad Sci U S A. 1969 Sep;64(1):155–160. doi: 10.1073/pnas.64.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hamlin C. R., Kohn R. R., Luschin J. H. Apparent accelerated aging of human collagen in diabetes mellitus. Diabetes. 1975 Oct;24(10):902–904. doi: 10.2337/diab.24.10.902. [DOI] [PubMed] [Google Scholar]
  18. Herbage D., Bouillet J., Bernengo J. C. Biochemical and physiochemical characterization of pepsin-solubilized type-II collagen from bovine articular cartilage. Biochem J. 1977 Feb 1;161(2):303–312. doi: 10.1042/bj1610303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kagwa-Nyanzi J. A. Les glycoprotéines tissulaires. Hypothèses concernant les memnbranes basales au cours du diabète. Presse Med. 1971 Nov 24;79(50):2277–2283. [PubMed] [Google Scholar]
  20. Kefalides N. A. Biochemical properties of human glomerular basement membrane in normal and diabetic kidneys. J Clin Invest. 1974 Feb;53(2):403–407. doi: 10.1172/JCI107573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kern P., Laurent M., Regnault F. Biochemical and ultrastructural studies of conjunctiva of hereditary diabetic mice. Rev Eur Etud Clin Biol. 1972 Nov;17(9):882–886. [PubMed] [Google Scholar]
  22. Kern P., Picard J., Caron M., Veissière D. Decreased binding of insulin to liver plasma membrane receptors in hereditary diabetic mice. Biochim Biophys Acta. 1975 May 6;389(2):281–289. doi: 10.1016/0005-2736(75)90321-1. [DOI] [PubMed] [Google Scholar]
  23. Kern P., Regnault F., Robert L. Biochemical and ultrastructural study of human diabetic conjunctiva. Biomedicine. 1976 Jan;24(1):32–39. [PubMed] [Google Scholar]
  24. Klein L., ChandraRajan J. Collagen degradation in rat skin but not in intestine during rapid growth: effect on collagen types I and III from skin. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1436–1439. doi: 10.1073/pnas.74.4.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lapiere C. M., Nusgens B., Pierard G. E. Interaction between collagen type I and type III in conditioning bundles organization. Connect Tissue Res. 1977;5(1):21–29. doi: 10.3109/03008207709152608. [DOI] [PubMed] [Google Scholar]
  26. Lenaers A., Lapiere C. M. Type III procollagen and collagen in skin. Biochim Biophys Acta. 1975 Jul 21;400(1):121–131. doi: 10.1016/0005-2795(75)90132-4. [DOI] [PubMed] [Google Scholar]
  27. Mahieu P. M., Winand R. J. Carbohydrate and amino-acid composition of human glomerular-basement-membrane fractions purified by affinity chromatography. Eur J Biochem. 1973 Aug 1;37(1):157–163. doi: 10.1111/j.1432-1033.1973.tb02970.x. [DOI] [PubMed] [Google Scholar]
  28. Malathy K., Kurup P. A. Metabolism of glycosaminoglycans in alloxan diabetic rats. I. Changes in tissue glycosaminoglycans. Diabetes. 1972 Dec;21(12):1162–1167. doi: 10.2337/diab.21.12.1162. [DOI] [PubMed] [Google Scholar]
  29. Meigel W. N., Gay S., Weber L. Dermal architecture and collagen type distribution. Arch Dermatol Res. 1977 Jul 21;259(1):1–10. doi: 10.1007/BF00562732. [DOI] [PubMed] [Google Scholar]
  30. Miller E. J. Biochemical characteristics and biological significance of the genetically-distinct collagens. Mol Cell Biochem. 1976 Dec 10;13(3):165–192. doi: 10.1007/BF01731779. [DOI] [PubMed] [Google Scholar]
  31. Miller E. J., Epstein E. H., Jr, Piez K. A. Identification of three genetically distinct collagens by cyanogen bromide cleavage of insoluble human skin and cartilage collagen. Biochem Biophys Res Commun. 1971 Mar 19;42(6):1024–1029. doi: 10.1016/0006-291x(71)90006-4. [DOI] [PubMed] [Google Scholar]
  32. Muller D. P., Harries J. T., Lloyd J. K. The relative importance of the factors involved in the absorption of vitamin E in children. Gut. 1974 Dec;15(12):966–971. doi: 10.1136/gut.15.12.966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nakamura M., Yamada K. Studies on a diabetic (KK) strain of the mouse. Diabetologia. 1967 Apr;3(2):212–221. doi: 10.1007/BF01222198. [DOI] [PubMed] [Google Scholar]
  34. Oppermann W., Iwatsuka H., Reddi A. S., Camerini-Davalos R. A. Prolonged fasting in mice: a more sensitive approach to genetic diabetes. Horm Res. 1975;6(3):150–156. doi: 10.1159/000178673. [DOI] [PubMed] [Google Scholar]
  35. Penttinen R. P., Lichtenstein J. R., Martin G. R., McKusick V. A. Abnormal collagen metabolism in cultured cells in osteogenesis imperfecta. Proc Natl Acad Sci U S A. 1975 Feb;72(2):586–589. doi: 10.1073/pnas.72.2.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pope F. M., Martin G. R., Lichtenstein J. R., Penttinen R., Gerson B., Rowe D. W., McKusick V. A. Patients with Ehlers-Danlos syndrome type IV lack type III collagen. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1314–1316. doi: 10.1073/pnas.72.4.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ramamurthy N. S., Zebrowski E. J., Golub L. M. The effect of alloxan diabetes on gingival collagen metabolism in rats. Arch Oral Biol. 1972 Nov;17(11):1551–1560. doi: 10.1016/0003-9969(72)90042-8. [DOI] [PubMed] [Google Scholar]
  38. Risteli J., Koivisto V. A., Akerblom H. K., Kivirikko K. I. Intracellular enzymes of collagen biosynthesis in rat kidney in streptozotocin diabetes. Diabetes. 1976 Nov;25(11):1066–1070. doi: 10.2337/diab.25.11.1066. [DOI] [PubMed] [Google Scholar]
  39. Robert L., Robert B., Moczar E., Moczar M. Les glycoprotéines de structure du tissu conjonctif. Pathol Biol (Paris) 1972 Dec;20(23):1001–1012. [PubMed] [Google Scholar]
  40. Rojkind M., González E. An improved method for determining specific radioactivities of proline-14C and hydroxyproline-14C in collagen and in noncollagenous proteins. Anal Biochem. 1974 Jan;57(1):1–7. doi: 10.1016/0003-2697(74)90043-8. [DOI] [PubMed] [Google Scholar]
  41. Scott P. G., Veis A. The cyanogen bromide peptides of bovine soluble and insoluble collagens. I. Characterization of peptides from soluble type I collagen by sodium dodecylsulphate polyacrylamide gel electrophoresis. Connect Tissue Res. 1976;4(2):107–116. doi: 10.3109/03008207609152206. [DOI] [PubMed] [Google Scholar]
  42. Shuttleworth C. A., Forrest L. Changes in guinea-pig dermal collagen during development. Eur J Biochem. 1975 Jul 1;55(2):391–395. doi: 10.1111/j.1432-1033.1975.tb02174.x. [DOI] [PubMed] [Google Scholar]
  43. Spiro R. G. Biochemistry of the renal glomerular basement membrane and its alterations in diabetes mellitus. N Engl J Med. 1973 Jun 21;288(25):1337–1342. doi: 10.1056/NEJM197306212882506. [DOI] [PubMed] [Google Scholar]
  44. Telner A., Kalant N. In vitro synthesis of aortic glycosaminoglycans. Effect of diet, lipoproteins and diabetes. Atherosclerosis. 1974 Jul-Aug;20(1):81–88. doi: 10.1016/0021-9150(74)90081-1. [DOI] [PubMed] [Google Scholar]
  45. Vracko R., Benditt E. P. Restricted replicative life-span of diabetic fibroblasts in vitro: its relation to microangiopathy. Fed Proc. 1975 Jan;34(1):68–70. [PubMed] [Google Scholar]
  46. Westberg N. G. Biochemical alterations of the human glomerular basement membrane in diabetes. Diabetes. 1976;25(2 Suppl):920–924. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES