Fibrosis regression is induced by AdhMMP8 in a murine model of chronic kidney injury

Adenoviral vector AdhMMP8 (human Metalloproteinase-8 cDNA) administration has been proven beneficial in various experimental models of liver injury improving liver function and decreasing fibrosis. In this study, we evaluated the potential therapeutic AdhMMP8 effect in a chronic kidney damage experi...

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Veröffentlicht in:PloS one 2020-12, Vol.15 (12), p.e0243307, Article 0243307
Hauptverfasser: Contreras-Salinas, Homero, Meza-Rios, Alejandra, Garcia-Banuelos, Jesus, Sandoval-Rodriguez, Ana, Sanchez-Orozco, Laura, Garcia-Benavides, Leonel, De la Rosa-Bibiano, Ricardo, Monroy Ramirez, Hugo Christian, Gutierrez-Cuevas, Jorge, Santos-Garcia, Arturo, Armendariz-Borunda, Juan
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Sprache:eng
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Zusammenfassung:Adenoviral vector AdhMMP8 (human Metalloproteinase-8 cDNA) administration has been proven beneficial in various experimental models of liver injury improving liver function and decreasing fibrosis. In this study, we evaluated the potential therapeutic AdhMMP8 effect in a chronic kidney damage experimental model. Chronic injury was induced by orogastric adenine administration (100mg/kg/day) to Wistar rats for 4 weeks. AdhMMP8 (3x10(11)vp/kg) was administrated in renal vein during an induced-ligation-ischemic period to facilitate kidney transduction causing no-additional kidney injury as determined by histology and serum creatinine. Animals were sacrificed at 7- and 14-days post-Ad injection. Fibrosis, histopathological features, serum creatinine (sCr), BUN, and renal mRNA expression of alpha SMA, Col-1 alpha, TGF-beta 1, CTGF, BMP7, IL-1, TNF alpha, VEGF and PAX2 were analyzed. Interestingly, AdhMMP8 administration resulted in cognate human MMP8 protein detection in both kidneys, whereas hMMP8 mRNA was detected only in the left kidney. AdhMMP8 significantly reduced kidney tubule-interstitial fibrosis and glomerulosclerosis. Also, tubular atrophy and interstitial inflammation were clearly decreased rendering improved histopathology, and down regulation of profibrogenic genes expression. Functionally, sCr and BUN were positively modified. The results showed that AdhMMP8 decreased renal fibrosis, suggesting that MMP8 could be a possible therapeutic candidate for kidney fibrosis treatment.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0243307