Aim: 

Alpha11 integrin (A11) is a collagen binding integrin important in myofibroblast differentiation and collagen fiber formation. It has not previously been studied in the kidney. Renal fibrosis is the final common pathway in chronic kidney disease regardless of original pathology. Unilateral urethral obstruction (UUO) is a well characterized model where the obstructed kidney quickly develops fibrosis.

Methods: 

A11 deficient mice (KO) and wild-type controls (WT) underwent UUO, and were left 1 week. 47 genes, with 18S RNA as standard, were analysed by real-time PCR, and renal damage was assessed histologically using picro-sirius red.

Results: 

ANOVA showed differential expression in 27 genes. Comparison of KO-control to WT-control, identified three differentially expressed genes (p< 0.05): Pdgfb (-0.84 log2 fold change), Col3a1 (-1.29) and Fmod (-0.83). 23 genes were differentially expressed in UUO vs. contra lateral kidney (CL) in WT, where of 22 were up regulated: Adamts1, Adamts2, Col1a1, Col1a2, Col3a1, Col4a1, Dcn, Fbln1, Fn1, Lgals3, Loxl1, Mmp2, Mmp3, Nid1, Pdgfa, Pdgfb, Spp1, Tgfb1, Timp1, Timp2, Trf, Vim. The only down regulated gene was Vegfb. 25 genes were differentially expressed in KO-UUO compared to KO-CL. The list was slightly different from WT mice: Nid1 was not significantly changed, while Vegfc, Itgav and Cola1 were all increased. Two genes were different between UUO-KO and UUO-WT: Pdgfb (0.88 log2FC), and Spp1 (0.64). Sirius red staining showed a significant increase in renal fibrosis in UUO kidneys, and UUO produced clear hydronephrosis with beginning atrophy and fibrosis after one week.

Conclusion: 

A11 deficient mice show lower baseline expression of Pdgfb and a stronger activation of Pdgfb and osteopontin (spp1) during development of fibrosis after UUO.