T Moriya1, T J Groppoli, Y Kim, M Mauer. 1. Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
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/microm2, 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/microm2 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.
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 diabeticpatients (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/microm2, 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/microm2 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 diabeticpatients 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.
Authors: Zhengtao Qin; Carl K Hoh; Emilia S Olson; Amin Haghighat Jahromi; David J Hall; Christopher V Barback; Young-Hyun You; Motoko Yanagita; Kumar Sharma; David R Vera Journal: J Nucl Med Date: 2019-02-22 Impact factor: 10.057