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MMP2 deficient mice are protected from hydronephrosis after unilateral urethral obstruction
Author(s) -
Tveitarås Maria Kathrine,
Skogstrand Trude,
Helle Frank,
Leh Sabine,
Reed Rolf K,
Chatziantoniou Christos,
Hultström Michael
Publication year - 2012
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.26.1_supplement.868.12
Subject(s) - hydronephrosis , mmp2 , mmp9 , sirius red , parenchyma , fibrosis , medicine , pathology , biology , downregulation and upregulation , gene , urinary system , biochemistry , cancer , metastasis
Matrix Metalloprotease 2 (Mmp2) is a collagenase known to be important in the development of renal fibrosis. In unilateral urethral obstruction the obstructed kidney (UUO) quickly develops fibrosis, while the contralateral (CL) does not. The fibrotic process in Mmp2 deficient mice (KO) was investigated using heterozygote (HZ) and wild‐type mice as controls (WT). UUO caused hydronephrosis, dilation of renal tubules, loss of parenchymal thickness, and fibrosis after one week. Sirius red quantification of fibrous collagen showed 0.13±0.03% positivity in CL and 0.33±0.05% in UUO (p<0.05). KO‐UUO developed less severe hydronephrosis and had preserved renal parenchyma. Out of 48 genes quantified by PCR 26 were differentially expressed by ANOVA (p<0.05). 25 genes were up‐regulated in UUO wild‐type mice: Adamts1, ‐2, Col1a1, ‐2, ‐3a1, ‐4a1, ‐5a1, ‐ 5a2, Dcn, Fbln1, ‐5, Fmod, Fn1, Itga2, Loxl1, Mgp, Mmp2, ‐3, Nid1, Pdgfb, Spp1, Tgfb1, Timp2, Trf, Vim. Only 18 genes were differentially expression in KO‐UUO. Mmp9 was up regulated, while Mmp2, Fn1, Loxl1, Col5a1, Fbln5, Fmod, Fbln1 and Col5a2 were not changed in KO‐UUO. In conclusion, Mmp2 KO protects against hydronephrosis after UUO and shows milder changes in gene expression compared to WT. The study was supported by the Western Health Authority of Norway, Magn. Bergvall foundation and Lars Hiertas Minne Foundation.