title: Decreased hypoxia-inducible factor-1α in gastrocnemius muscle in rats with chronic kidney disease.
abstract: OBJECTIVE
  Hypoxia-inducible factor (HIF)-1α is responsible for increased expression of genes engaged in angiogenesis. Our previous study indicated capillary rarefaction and atrophy of glycolytic fibers, mainly in locomotor muscles of uremic animals. Perhaps these changes are secondary to disturbances of HIF-1α in skeletal muscles.
  
  
  METHODS
  Expression of HIF-1α at mRNA and protein levels, as well as mRNA of vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), in gastrocnemius muscle (MG) and longissimus thoracic muscle (ML) were measured by RT-PCR and Western blot. Rats were randomized to subtotal nephrectomy (CKD5/6), uninephrectomy (CKD1/2) or sham operation (controls).
  
  
  RESULTS
  For CKD5/6 versus controls, mRNA levels for HIF-1α, VEGF-A, VEGFR-1 and VEGFR-2 were significantly reduced only in MG, while eNOS was significantly decreased and iNOS was significantly increased only in ML. Western blot analysis indicated significantly increased HIF-1α protein levels in MG and ML from CKD1/2 animals versus controls, whereas in the CKD5/6 group, the level of HIF-1α protein decreased significantly in MG and increased significantly in ML versus controls and CKD1/2.
  
  
  CONCLUSIONS
  The reduced expression of HIF-1α mRNA and protein in locomotor muscle from CKD5/6 animals may be involved in the pathogenesis of uremic myopathy. Increased expression of iNOS in the postural muscles may act as a protective factor through HIF-1α stabilization.
authors.affiliation: Department of Nephrology, Hypertension and Internal Diseases, Collegium Medicum of Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland. flis3 @ wp.pl
authors.forename: Mariusz
authors.initials: M
authors.lastname: Flisiński
authors.forename: Andrzej
authors.initials: A
authors.lastname: Brymora
authors.forename: Irena
authors.initials: I
authors.lastname: Bartłomiejczyk
authors.forename: Ewa
authors.initials: E
authors.lastname: Wiśniewska
authors.forename: Ryszard
authors.initials: R
authors.lastname: Gołda
authors.forename: Anna
authors.initials: A
authors.lastname: Stefańska
authors.forename: Leszek
authors.initials: L
authors.lastname: Pączek
authors.forename: Jacek
authors.initials: J
authors.lastname: Manitius
mesh_terms: D000818:Animals; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger