Expression of profibrotic genes in a murine remnant kidney model.
OBJECTIVE
To test the hypothesis that there is increased expression of several profibrotic genes, including matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2), a disintegrin and metalloproteinase with thrombospondin motif-1 (ADAMTS-1), and fibroblast specific protein-1 (FSP-1) in a murine remnant kidney model.


METHODS
Chronic kidney disease (CKD) was created in 10 C57BL/6 male mice (20-25 g) by performing a right nephrectomy and ligation of the upper pole of the left kidney (remnant kidney). Animals were sacrificed 42 days and 56 days later. Reverse transcriptase polymerase chain reaction (RT-PCR) for MMP-2, MMP-9, TIMP-1, TIMP-2, ADAMTS-1, and FSP-1 was performed in the remnant kidney. Histologic evaluation of the remnant kidney was performed using Ki-67, α-smooth muscle cell actin (α-SMA), hematoxylin and eosin, and Masson' trichrome staining. Kidney function was assessed using serum blood urea nitrogen (BUN) and creatinine.


RESULTS
The mean serum BUN and creatinine levels at day 42 and day 56 were significantly higher than baseline (P < .05). By day 42, the mean expression of MMP-2, MMP-9, TIMP-1, ADAMTS-1, and FSP-1 was significantly higher in the remnant kidney compared with the normal kidney (P < .05); by day 56, only FSP-1 expression was significantly higher (P < .05). There was increased fibrosis by Masson' trichrome, increased Ki-67, and increased α-SMA staining in the remnant kidney compared with the normal kidney.


CONCLUSIONS
In the remnant kidney, there was increased fibrosis with increased α-SMA and Ki-67 staining and significantly increased expression of MMP-2, MMP-9, TIMP-1, ADAMTS-1, and FSP-1.
Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA.
Binxia
B
Yang
Pawan K
PK
Vohra
Rajiv
R
Janardhanan
Khamal D
KD
Misra
Sanjay
S
Misra
D051722:ADAM Proteins / Q000378:metabolism*; D000818:Animals; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D019714:Tissue Inhibitor of Metalloproteinases; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases