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Effects of high salt diet on expression of extracellular matrix (ECM) proteins and matrix metalloproteases (MMP) in obese Zucker rat
Author(s) -
Dong Jun,
Habibi Shagayeg,
Benakenakare Indira,
Pamidimukkala Jaya
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a338-c
Subject(s) - extracellular matrix , matrix metalloproteinase , downregulation and upregulation , proteases , plasminogen activator , endocrinology , medicine , kidney , chemistry , enzyme , biochemistry , gene
The obese Zucker rat is a widely studied model of renal disease associated with metabolic syndrome. These rats are insulin resistant, dyslipidemic and hypertensive early on and these symptoms worsen with age. High salt diet not only aggravates hypertension but also the progression of renal injury in this model. A key factor in the progression of renal disease is the accumulation of ECM proteins in the renal tissue. The objective of the present study is to comprehensively assess the changes in expression of all known ECM proteins and proteolytic enzymes using a rat ECM and adhesion molecule microarray( Supearray®). Methods: Nine week old male and female Zucker rats (n=6) were placed on high salt diet for 1 week, and the kidneys removed for RNA isolation. After purifying to obtain array grade RNA,Truelabeling AMP kit ® was used for linear amplification of the message and to synthesize labeled antisense RNA (cRNA). The labeled cRNA was then hybridized to the array overnight and subjected to several washing steps prior to imaging. Results: High salt diet caused significant upregulation in the expression of ECM protein collagen type 1 alpha1 and membrane associated MMPs, MMP14 and 1a. In addition, other tissue and serum proteases involved in ECM degradation such as lymphoyte specific selectin, tissue plasminogen activator and plasminogen urokinase were also upregulated in the high salt groups. In conclusion, high salt diet appears to facilitate progression of renal disease in the obese Zucker rats by activating specific components of tissue injury and repair process. Supported by NASA‐MU (NAG5‐12300) Partnership for Understanding Sex differences in Physiology, AHA Beg Grant‐in‐Aid and CA‐86916A.