RGD Reference Report - Role of fibrillin-1 in hypertensive and diabetic glomerular disease. - Rat Genome Database

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Role of fibrillin-1 in hypertensive and diabetic glomerular disease.

Authors: Hartner, A  Schaefer, L  Porst, M  Cordasic, N  Gabriel, A  Klanke, B  Reinhardt, DP  Hilgers, KF 
Citation: Hartner A, etal., Am J Physiol Renal Physiol. 2006 Jun;290(6):F1329-36. Epub 2005 Dec 27.
RGD ID: 7365080
Pubmed: PMID:16380460   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.00284.2005   (Journal Full-text)

The microfibrillar protein fibrillin-1 is a component of the mesangial matrix. Defects in fibrillin-1 predisposes individuals to vascular damage in Marfan syndrome, but the role of fibrillin-1 in kidney disease is unknown. We hypothesized that fibrillin-1 is involved in hypertensive or diabetic glomerular disease. DOCA-salt hypertension or streptozotocin (STZ) diabetes led to a significant increase in glomerular fibrillin-1 deposition. To test the functional role of fibrillin-1, DOCA hypertension and STZ diabetes were induced in mice homozygous for a mutation leading to a fivefold lower expression of fibrillin-1 (mgR/mgR). Untreated male mgR/mgR mice usually die from aortic dissection during the first 4 mo of life. All DOCA-treated mgR/mgR mice died within 2 wk after onset of DOCA treatment. DOCA-treated heterozygous (mgR/+) and their wild-type littermates displayed similar blood pressure levels, but albuminuria was significantly lower in mgR/+ than in wild-type mice after DOCA treatment. Similarly, STZ diabetic mgR/mgR and mgR/+ developed lower albuminuria than wild-type mice despite higher blood glucose levels in mgR/mgR and mgR/+ compared with wild-type mice. Blood pressure, blood glucose, and albuminuria did not differ among untreated mgR/mgR, mgR/+, and wild-type mice, respectively. In diabetic mgR/+ and mgR/mgR, but not in wild-type mice, an induction of glomerular decorin expression was observed. Thus underexpression of fibrillin-1 predisposes individuals to lethal aortic dissection in the presence of hypertension. On the other hand, albuminuria as a parameter of microvascular damage in hypertension and diabetes was ameliorated in fibrillin-1-underexpressing mice, possibly due to a compensatory upregulation of decorin. We conclude that fibrillin-1 may contribute to glomerular damage in hypertensive and diabetic kidney disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Albuminuria  ISOFbn1 (Mus musculus)7365080; 7365080associated with HypertensionRGD 
Albuminuria  IMP 7365080associated with HypertensionRGD 
Diabetic Nephropathies  ISOFbn1 (Mus musculus)7365080; 7365080associated with Diabetes Mellitus and ExperimentalRGD 
Diabetic Nephropathies  IMP 7365080associated with Diabetes Mellitus and ExperimentalRGD 
Experimental Diabetes Mellitus  ISOFbn1 (Rattus norvegicus)7365080; 7365080protein:increased expression:renal glomerulus (rat)RGD 
Experimental Diabetes Mellitus  IEP 7365080protein:increased expression:renal glomerulus (rat)RGD 
glomerulosclerosis  ISOFbn1 (Mus musculus)7365080; 7365080associated with HypertensionRGD 
glomerulosclerosis  IMP 7365080associated with HypertensionRGD 
hypertension  ISOFbn1 (Rattus norvegicus)7365080; 7365080protein:increased expression:renal glomerulus (rat)RGD 
hypertension  IEP 7365080protein:increased expression:renal glomerulus (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fbn1  (fibrillin 1)

Genes (Mus musculus)
Fbn1  (fibrillin 1)

Genes (Homo sapiens)
FBN1  (fibrillin 1)


Additional Information