Linked Life Data

16775606

Source:http://linkedlifedata.com/resource/pubmed/id/16775606

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-7-27
pubmed:abstractText
Excessive glomerular collagen IV and reactive oxygen species (ROS) production are key factors in the development of diabetic nephropathy. Integrin alpha1beta1, the major collagen IV receptor, dowregulates collagen IV and ROS production, suggesting this integrin might determine the severity of diabetic nephropathy. To test this possibility, wild-type and integrin alpha1-null mice were rendered diabetic with streptozotocin (STZ) (100 mg/kg single intraperitoneal injection), after which glomerular filtration rate (GFR), glomerular collagen deposition, and glomerular basement membrane (GBM) thickening were evaluated. In addition, ROS and collagen IV production by mesangial cells as well as their proliferation was measured in vitro. Diabetic alpha1-null mice developed worse renal disease than diabetic wild-type mice. A significant increase in GFR was evident in the alpha1-null mice at 6 weeks after the STZ injection; it started to decrease by week 24 and reached levels of non-diabetic mice by week 36. In contrast, GFR only increased in wild-type mice at week 12 and its elevation persisted throughout the study. Diabetic mutant mice also showed increased glomerular deposition of collagen IV and GBM thickening compared to diabetic wild-type mice. Primary alpha1-null mesangial cells exposed to high glucose produced more ROS than wild-type cells, which led to decreased proliferation and increased collagen IV synthesis, thus mimicking the in vivo finding. In conclusion, this study suggests that lack of integrin alpha1beta1 exacerbates the glomerular injury in a mouse model of diabetes by modulating GFR, ROS production, cell proliferation, and collagen deposition.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
460-70
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:16775606-Animals, pubmed-meshheading:16775606-Basement Membrane, pubmed-meshheading:16775606-Cell Division, pubmed-meshheading:16775606-Cell Movement, pubmed-meshheading:16775606-Cells, Cultured, pubmed-meshheading:16775606-Collagen Type IV, pubmed-meshheading:16775606-Diabetes Mellitus, Experimental, pubmed-meshheading:16775606-Diabetic Nephropathies, pubmed-meshheading:16775606-Disease Models, Animal, pubmed-meshheading:16775606-Glomerular Filtration Rate, pubmed-meshheading:16775606-Glucose, pubmed-meshheading:16775606-Glycosylation End Products, Advanced, pubmed-meshheading:16775606-Integrin alpha1, pubmed-meshheading:16775606-Integrin alpha1beta1, pubmed-meshheading:16775606-Male, pubmed-meshheading:16775606-Mesangial Cells, pubmed-meshheading:16775606-Mice, pubmed-meshheading:16775606-Mice, Inbred BALB C, pubmed-meshheading:16775606-Mice, Knockout, pubmed-meshheading:16775606-Oxidative Stress, pubmed-meshheading:16775606-Reactive Oxygen Species
pubmed:year
2006
pubmed:articleTitle
Glomerular injury is exacerbated in diabetic integrin alpha1-null mice.
pubmed:affiliation
Department of Medicine, Division of Nephrology, Medical Center North, Vanderbilt University, Nashville, Tennessee 37232, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural