Figure 6.

The fibrogenic pathways in the glomerular injury model are primarily regulated by YB-1. (a) Experimental design to induce nephrotoxic serum nephritis in wild-type (n = 3–5) and Ybx1^ΔRosaERT+TX (n = 3–5) mice following tamoxifen application. Three-month-old mice were gavaged with tamoxifen 28 days before NTS application to induce Ybx1 knockout. Nephrotoxic serum nephritis (NTS) was induced by the injection of sheep anti-rat glomerular immunoglobulins. Kidneys were analyzed on days 4 and 10 following disease induction. (b) No structural differences are seen between the healthy glomeruli of wild-type and Ybx1^ΔRosaERT+TX knockout mice, visualized by PAS staining. Scale bar, 50 µm. (c) Proteinuria were analyzed before and on days 4 and 10 following NTS injection. (d) Wild-type animals developed enhanced glomerular injury with the formation of extracapillary proliferates (crescents) as well as (e) enhanced fibrinogen deposition and exudation compared to Ybx1^ΔRosaERT+TX knockout mice following NTS injection. (f) Within the kidney tissue of wild-type mice, the transcripts of TAZ and the target genes thereof were increased following NTS injection compared to control kidneys. Amongst these, PAI1, Ankrd1, and CCN2 were less abundant in the kidneys of Ybx1^ΔRosaERT+TX knockout mice compared to wild-type animals following NTS. The Cyr61 and EGR1 transcript numbers were similar in both animal models. (* values > 1 represent significant changes) (g) Representative renal immunohistochemistry staining of Klotho in healthy and diseased kidney tissues of wild-type and Ybx1^ΔRosaERT+TX animals. (*** p < 0.001).