ArticlePloS one2015
Matrix Metalloproteinase-2 Knockout and Heterozygote Mice Are Protected from Hydronephrosis and Kidney Fibrosis after Unilateral Ureteral Obstruction.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Case Report: Giant congenital hydronephrosis presenting as massive retroperitoneal cystic lesion with literature review.Frontiers in surgery · 2026Article
- Kidney-specific delivery of a matrix metalloproteinase-2 inhibitory peptide fused to elastin-like polypeptide reduces proteinuria and renal fibrosis in a model of salt-sensitive hypertension.The Journal of pharmacology and experimental therapeutics · 2025Article
- Review
- Integrating network pharmacology and transcriptomics to identify solasonine's anti-osteosarcoma targets and experimental validation.Frontiers in oncology · 2025Article
- Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets.Journal of clinical medicine · 2024Review
- Expression of tissue fibrosis genes in congenitally obstructed pyeloureteral junction and biomarkers of renal damage.Central European journal of urology · 2024Article
- Therapeutic mechanism of baicalein in peritoneal dialysis-associated peritoneal fibrosis based on network pharmacology and experimental validation.Frontiers in pharmacology · 2023Article
- Serum matrix metalloproteinase 7 and accelerated glomerular filtration rate decline in a general non-diabetic population.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022Article
- Role of matrix metalloprotease-2 and MMP-9 in experimental lung fibrosis in mice.Respiratory research · 2022Article
- Evaluation of PGP 9.5, NGFR, TGFβ1, FGFR1, MMP-2, AT2R2, SHH, and TUNEL in Primary Obstructive Megaureter Tissue.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- Role of MMP-2 and CD147 in kidney fibrosis.Open life sciences · 2022Review
- Identification of novel therapeutic targets for contrast induced acute kidney injury (CI-AKI): alpha blockers as a therapeutic strategy for CI-AKI.Translational research : the journal of laboratory and clinical medicine · 2021Article
- Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Key metalloproteinase-mediated pathways in the kidney.Nature reviews. Nephrology · 2021Review
- You Say You Want a Resolution (of Fibrosis).American journal of respiratory cell and molecular biology · 2020Review
- Genetic or pharmacologic blockade of enhancer of zeste homolog 2 inhibits the progression of peritoneal fibrosis.The Journal of pathology · 2020Article
- Selected Metal Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases as Potential Biomarkers for Tubulointerstitial Fibrosis in Children with Unilateral Hydronephrosis.Disease markers · 2020Article
- AXL targeting reduces fibrosis development in experimental unilateral ureteral obstruction.Physiological reports · 2019Article
- Tyrphostin AG490 reduces inflammation and fibrosis in neonatal obstructive nephropathy.PloS one · 2019Article
- CERA Attenuates Kidney Fibrogenesis in the db/db Mouse by Influencing the Renal Myofibroblast Generation.Journal of clinical medicine · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matrix Metalloproteinase-2 (Mmp2) is a collagenase known to be important in the development of renal fibrosis. In unilateral ureteral obstruction (UUO) the obstructed kidney (OK) develops fibrosis, while the contralateral (CL) does not. In this study we investigated the effect of UUO on gene expression, fibrosis and pelvic remodeling in the kidneys of Mmp2 deficient mice (Mmp2-/-), heterozygous animals (Mmp2+/-) and wild-type mice (Mmp2+/+). Sham operated animals served as controls (Cntrl). UUO was prepared under isoflurane anaesthesia, and the animals were sacrificed after one week. UUO caused hydronephrosis, dilation of renal tubules, loss of parenchymal thickness, and fibrosis. Damage was most severe in Mmp2+/+ mice, while both Mmp2-/- and Mmp2+/- groups showed considerably milder hydronephrosis, no tubular necrosis, and less tubular dilation. Picrosirius red quantification of fibrous collagen showed 1.63±0.25% positivity in OK and 0.29±0.11% in CL (p<0.05) of Mmp2+/+, Mmp2-/- OK and Mmp2-/- CL exhibited only 0.49±0.09% and 0.23±0.04% (p<0.05) positivity, respectively. Mmp2+/- OK and Mmp2+/- CL showed 0.43±0.09% and 0.22±0.06% (p<0.05) positivity, respectively. Transcriptomic analysis showed that 26 genes (out of 48 examined) were differentially expressed by ANOVA (p<0.05). 25 genes were upregulated in Mmp2+/+ OK compared to Mmp2+/+ CL: 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. In Mmp2-/- and Mmp2+/- 18 and 12 genes were expressed differentially between OK and CL, respectively. Only Mmp2 was differentially regulated when comparing Mmp2-/- OK and Mmp2+/- OK. Under stress, it appears that Mmp2+/- OK responds with less Mmp2 upregulation than Mmp2+/+ OK, suggesting that there is a threshold level of Mmp2 necessary for damage and fibrosis to occur. In conclusion, reduced Mmp2 expression during UUO protects mice against hydronephrosis and renal fibrosis.
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