Regulation of renal laminin in mice with type II diabetes.
This study examines the regulation of renal laminin in the db/db mouse, a model of type II diabetes characterized by extensive remodeling of extracellular matrix. Immunohistochemistry demonstrated an increase in the contents of laminin chains including beta1 chain in the mesangium and tubular basement membranes at 1, 2, 3, and 4 mo of diabetes. Immunofluorescence with an antibody against the recently discovered laminin alpha5 chain showed that in the normal mouse, the protein had a restricted distribution to the glomerular and tubular basement membranes with scant expression in the mesangium of older mice. In the diabetic mouse, the laminin alpha5 chain content of the glomerular and tubular basement membranes was increased, with marked expression in the mesangium. Northern analysis revealed a significant decrease in the renal cortical contents of alpha5, beta1, and gamma1 chain mRNA in the diabetic mice compared to control, at each of the time points. In situ hybridization showed decreased abundance of alpha5 transcripts in the glomeruli of diabetic mice compared to nondiabetic controls. Analysis of mRNA changes by Northern and in situ hybridization studies demonstrated that the reduction in laminin transcripts involved both glomerular and tubular elements. These observations demonstrate that laminin accumulation in the db/db mice with type II diabetes is due to nontranscriptional mechanisms. Because previous investigations in rodents with type I diabetes have shown that the increase in renal laminin content was associated with a corresponding increment in laminin chain transcript levels, it appears that the mechanisms underlying augmentation in renal matrix laminin content may be distinct in the two types of diabetes.
Ha
T S
TS
Department of Medicine, University of Texas Health Science Center and A.L. Murphy Veterans' Administration Hospital, San Antonio 78284, USA.
Barnes
J L
JL
Stewart
J L
JL
Ko
C W
CW
Miner
J H
JH
Abrahamson
D R
DR
Sanes
J R
JR
Kasinath
B S
BS
D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007797:Laminin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D007797:Laminin; D012333:RNA, Messenger; D003094:Collagen