Quantitative immunoelectron microscopy of type VI collagen in glomeruli in type I diabetic patients

T. Moriya, T. J. Groppoli, Youngki Kim, Michael Mauer

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: The nature of the extracellular matrix (ECM) accumulating in the glomerular basement membrane (GBM) and mesangium (Mes) in diabetes is unknown. Type IV collagen (Col IV) as estimated by quantitative immunoelectron microscopy was reduced in type I diabetic patients (D) with rapid ("fast-track") compared with slow ("slow-track") development of diabetic nephropathy (DN) lesions and controls (C). Col VI is another ECM component suggested to account for Mes matrix (MM) expansion in DN. Methods: Col VI ECM density was evaluated in eight "slow-track" (Mes fractional volume [Vv(Mes/glom)] <0.32, duration >20 years) and seven "fast-track" patients [Vv(Mes/glom) >0.37, duration <20 years diabetes] and in eight C. Quantitative immunoelectron microscopy was performed using polyclonal antibodies to Col VI. Gold particle density (PDG) in MM and the inner layer (IL) of the GBM was measured using stereologic methods. Results: GBM IL PDG was decreased in both fast-track (1.7 ± 1.6/μm2, mean ± SD, P < 0.002) and slow-track (3.9 ± 2.4, P < 0.02) D versus C (10.8 ± 7.9). GBM IL PDG was also lower in the fast-track versus slow-track D (P < 0.04). Mes matrix PDG/μm2 was decreased in fast-track D (3.2 ± 3.6) versus C (14.1 ± 14.6, P < 0.02); a similar trend was seen in slow-track D (5.7 ± 5.6, P < 0.1). There was no significant difference in MM PDG between the slow-track and fast-track D. Conclusion: Col VI density in MM and GBM is decreased in diabetic patients with slowly and rapidly developing renal lesions. This leaves the nature of ECM accumulation in DN unexplained. At least in part, glomerular ECM compositional change is related to diabetes per se and may be independent of the severity of lesions.

Original languageEnglish (US)
Pages (from-to)317-323
Number of pages7
JournalKidney International
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2001

Fingerprint

Collagen Type VI
Glomerular Basement Membrane
Immunoelectron Microscopy
Extracellular Matrix
Diabetic Nephropathies
Dilatation and Curettage
Collagen Type IV
Gold
Kidney
Antibodies

Keywords

  • Extracellular matrix
  • Glomerular basement membrane
  • Gold particle density
  • Insulin-dependent diabetes mellitus
  • Mesangial matrix
  • Renal lesions

Cite this

Quantitative immunoelectron microscopy of type VI collagen in glomeruli in type I diabetic patients. / Moriya, T.; Groppoli, T. J.; Kim, Youngki; Mauer, Michael.

In: Kidney International, Vol. 59, No. 1, 01.01.2001, p. 317-323.

Research output: Contribution to journalArticle

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abstract = "Background: The nature of the extracellular matrix (ECM) accumulating in the glomerular basement membrane (GBM) and mesangium (Mes) in diabetes is unknown. Type IV collagen (Col IV) as estimated by quantitative immunoelectron microscopy was reduced in type I diabetic patients (D) with rapid ({"}fast-track{"}) compared with slow ({"}slow-track{"}) development of diabetic nephropathy (DN) lesions and controls (C). Col VI is another ECM component suggested to account for Mes matrix (MM) expansion in DN. Methods: Col VI ECM density was evaluated in eight {"}slow-track{"} (Mes fractional volume [Vv(Mes/glom)] <0.32, duration >20 years) and seven {"}fast-track{"} patients [Vv(Mes/glom) >0.37, duration <20 years diabetes] and in eight C. Quantitative immunoelectron microscopy was performed using polyclonal antibodies to Col VI. Gold particle density (PDG) in MM and the inner layer (IL) of the GBM was measured using stereologic methods. Results: GBM IL PDG was decreased in both fast-track (1.7 ± 1.6/μm2, mean ± SD, P < 0.002) and slow-track (3.9 ± 2.4, P < 0.02) D versus C (10.8 ± 7.9). GBM IL PDG was also lower in the fast-track versus slow-track D (P < 0.04). Mes matrix PDG/μm2 was decreased in fast-track D (3.2 ± 3.6) versus C (14.1 ± 14.6, P < 0.02); a similar trend was seen in slow-track D (5.7 ± 5.6, P < 0.1). There was no significant difference in MM PDG between the slow-track and fast-track D. Conclusion: Col VI density in MM and GBM is decreased in diabetic patients with slowly and rapidly developing renal lesions. This leaves the nature of ECM accumulation in DN unexplained. At least in part, glomerular ECM compositional change is related to diabetes per se and may be independent of the severity of lesions.",
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AU - Groppoli, T. J.

AU - Kim, Youngki

AU - Mauer, Michael

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Y1 - 2001/1/1

N2 - Background: The nature of the extracellular matrix (ECM) accumulating in the glomerular basement membrane (GBM) and mesangium (Mes) in diabetes is unknown. Type IV collagen (Col IV) as estimated by quantitative immunoelectron microscopy was reduced in type I diabetic patients (D) with rapid ("fast-track") compared with slow ("slow-track") development of diabetic nephropathy (DN) lesions and controls (C). Col VI is another ECM component suggested to account for Mes matrix (MM) expansion in DN. Methods: Col VI ECM density was evaluated in eight "slow-track" (Mes fractional volume [Vv(Mes/glom)] <0.32, duration >20 years) and seven "fast-track" patients [Vv(Mes/glom) >0.37, duration <20 years diabetes] and in eight C. Quantitative immunoelectron microscopy was performed using polyclonal antibodies to Col VI. Gold particle density (PDG) in MM and the inner layer (IL) of the GBM was measured using stereologic methods. Results: GBM IL PDG was decreased in both fast-track (1.7 ± 1.6/μm2, mean ± SD, P < 0.002) and slow-track (3.9 ± 2.4, P < 0.02) D versus C (10.8 ± 7.9). GBM IL PDG was also lower in the fast-track versus slow-track D (P < 0.04). Mes matrix PDG/μm2 was decreased in fast-track D (3.2 ± 3.6) versus C (14.1 ± 14.6, P < 0.02); a similar trend was seen in slow-track D (5.7 ± 5.6, P < 0.1). There was no significant difference in MM PDG between the slow-track and fast-track D. Conclusion: Col VI density in MM and GBM is decreased in diabetic patients with slowly and rapidly developing renal lesions. This leaves the nature of ECM accumulation in DN unexplained. At least in part, glomerular ECM compositional change is related to diabetes per se and may be independent of the severity of lesions.

AB - Background: The nature of the extracellular matrix (ECM) accumulating in the glomerular basement membrane (GBM) and mesangium (Mes) in diabetes is unknown. Type IV collagen (Col IV) as estimated by quantitative immunoelectron microscopy was reduced in type I diabetic patients (D) with rapid ("fast-track") compared with slow ("slow-track") development of diabetic nephropathy (DN) lesions and controls (C). Col VI is another ECM component suggested to account for Mes matrix (MM) expansion in DN. Methods: Col VI ECM density was evaluated in eight "slow-track" (Mes fractional volume [Vv(Mes/glom)] <0.32, duration >20 years) and seven "fast-track" patients [Vv(Mes/glom) >0.37, duration <20 years diabetes] and in eight C. Quantitative immunoelectron microscopy was performed using polyclonal antibodies to Col VI. Gold particle density (PDG) in MM and the inner layer (IL) of the GBM was measured using stereologic methods. Results: GBM IL PDG was decreased in both fast-track (1.7 ± 1.6/μm2, mean ± SD, P < 0.002) and slow-track (3.9 ± 2.4, P < 0.02) D versus C (10.8 ± 7.9). GBM IL PDG was also lower in the fast-track versus slow-track D (P < 0.04). Mes matrix PDG/μm2 was decreased in fast-track D (3.2 ± 3.6) versus C (14.1 ± 14.6, P < 0.02); a similar trend was seen in slow-track D (5.7 ± 5.6, P < 0.1). There was no significant difference in MM PDG between the slow-track and fast-track D. Conclusion: Col VI density in MM and GBM is decreased in diabetic patients with slowly and rapidly developing renal lesions. This leaves the nature of ECM accumulation in DN unexplained. At least in part, glomerular ECM compositional change is related to diabetes per se and may be independent of the severity of lesions.

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KW - Glomerular basement membrane

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KW - Insulin-dependent diabetes mellitus

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KW - Renal lesions

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