J Østergaard1, S Thiel, M Gadjeva, T K Hansen, R Rasch, A Flyvbjerg. 1. The Medical Research Laboratories, Clinical Institute and Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark.
Abstract
AIMS/HYPOTHESIS: An increasing amount of evidence indicates that mannose-binding lectin (MBL) plays a role in the development of diabetic nephropathy. The main objective of the study was to analyse whether MBL influences the effects of diabetes on the kidneys. MATERIALS AND METHODS: In one group of wild-type mice and in one group of MBL double knockout mice we induced diabetes by the use of streptozotocin as a model of type 1 diabetes. Two groups of non-diabetic mice, wild-type and MBL knockout, were also included. By two-way ANOVA we evaluated if MBL modulated the effects of diabetes by testing the interaction between diabetes and MBL. RESULTS: MBL interacted with the effects of diabetes on three outcome measures: kidney weight (p < 0.001), urinary albumin excretion (p = 0.001) and the expression of collagen IV alpha 1 (Col4a1) mRNA (p = 0.002). This means that the effects that diabetes normally has on these parameters were significantly modified by MBL. MBL showed a tendency to interact with the effects of diabetes on glomerular basement membrane thickness and total mesangial volume (p = 0.065 and p = 0.063, respectively). Glomerular volume and total mesangial volume were significantly smaller in animals lacking MBL than in wild-type animals (p = 0.006 and p = 0.047, respectively). CONCLUSIONS/ INTERPRETATION: These findings, for the first time, show that the degree of kidney alteration as a consequence of diabetes is modified by MBL. These findings support a pivotal role of MBL in the development of diabetic kidney disease.
AIMS/HYPOTHESIS: An increasing amount of evidence indicates that mannose-binding lectin (MBL) plays a role in the development of diabetic nephropathy. The main objective of the study was to analyse whether MBL influences the effects of diabetes on the kidneys. MATERIALS AND METHODS: In one group of wild-type mice and in one group of MBL double knockout mice we induced diabetes by the use of streptozotocin as a model of type 1 diabetes. Two groups of non-diabeticmice, wild-type and MBL knockout, were also included. By two-way ANOVA we evaluated if MBL modulated the effects of diabetes by testing the interaction between diabetes and MBL. RESULTS:MBL interacted with the effects of diabetes on three outcome measures: kidney weight (p < 0.001), urinary albumin excretion (p = 0.001) and the expression of collagen IV alpha 1 (Col4a1) mRNA (p = 0.002). This means that the effects that diabetes normally has on these parameters were significantly modified by MBL. MBL showed a tendency to interact with the effects of diabetes on glomerular basement membrane thickness and total mesangial volume (p = 0.065 and p = 0.063, respectively). Glomerular volume and total mesangial volume were significantly smaller in animals lacking MBL than in wild-type animals (p = 0.006 and p = 0.047, respectively). CONCLUSIONS/ INTERPRETATION: These findings, for the first time, show that the degree of kidney alteration as a consequence of diabetes is modified by MBL. These findings support a pivotal role of MBL in the development of diabetic kidney disease.
Authors: M Saraheimo; C Forsblom; T K Hansen; A-M Teppo; J Fagerudd; K Pettersson-Fernholm; S Thiel; L Tarnow; P Ebeling; A Flyvbjerg; P-H Groop Journal: Diabetologia Date: 2004-12-23 Impact factor: 10.122
Authors: Dae Ryong Cha; Young Sun Kang; Sang Youb Han; Yi Hwa Jee; Kum Hyun Han; Jee Young Han; Young Sik Kim; Nan Hee Kim Journal: J Endocrinol Date: 2004-10 Impact factor: 4.286
Authors: Edward D Verrier; Stanton K Shernan; Kenneth M Taylor; Frans Van de Werf; Mark F Newman; John C Chen; Michel Carrier; Axel Haverich; Kevin J Malloy; Peter X Adams; Thomas G Todaro; Christopher F Mojcik; Scott A Rollins; Jerrold H Levy Journal: JAMA Date: 2004-05-19 Impact factor: 56.272
Authors: Jakob A Østergaard; Steffen Thiel; Peter Hovind; Charlotte B Holt; Hans-Henrik Parving; Allan Flyvbjerg; Peter Rossing; Troels K Hansen Journal: Diabetologia Date: 2014-07-28 Impact factor: 10.122
Authors: T K Hansen; C Forsblom; M Saraheimo; L Thorn; J Wadén; P Høyem; J Østergaard; A Flyvbjerg; P-H Groop Journal: Diabetologia Date: 2010-04-16 Impact factor: 10.122
Authors: Yunhua L Muller; Robert L Hanson; Li Bian; Janel Mack; Xiaolian Shi; Ruth Pakyz; Alan R Shuldiner; William C Knowler; Clifton Bogardus; Leslie J Baier Journal: Diabetes Date: 2010-06-03 Impact factor: 9.461
Authors: M A Siezenga; P K Chandie Shaw; R N van der Geest; T E Mollnes; M R Daha; T J Rabelink; S P Berger Journal: Clin Exp Immunol Date: 2009-07 Impact factor: 4.330
Authors: Mari A Kaunisto; Lisa Sjölind; Riitta Sallinen; Kim Pettersson-Fernholm; Markku Saraheimo; Sara Fröjdö; Carol Forsblom; Johan Fagerudd; Troels K Hansen; Allan Flyvbjerg; Maija Wessman; Per-Henrik Groop Journal: Diabetes Date: 2009-04-14 Impact factor: 9.461