LRP-1 mediates the proliferative effect of tPA. A: tPA failed to induce cell growth in LRP-1–deficient fibroblasts. Mouse fibroblasts MEF-1 (LRP-1+/+) and PEA-13 (LRP-1−/−) were treated with 10 nmol/L tPA for 48 hours, and cell growth was assessed by WST-8 assay. *P < 0.05, n = 4. Deficiency of LRP-1 in PEA-13 cells was confirmed by Western blot (A, inset). NRK-49F cells were transfected with either control siRNA (consiRNA) or LRP-1–specific siRNA (LRP-1siRNA), followed by treatment with tPA (10 nmol/L) as indicated. Knockdown of LRP-1 in NRK-49F cells by siRNA inhibition abrogated tPA-induced GSK3β phosphorylation (B) and cell proliferation (C). **P < 0.01, n = 4.