INSIG1 and renal fibrosis: Because fibroblast activation plays a crucial role in renal fibrosis, we created fibroblast-specific Insig1-knockout (Insig1ΔS100A4) mice, which had ~85% reduction in Insig1 expression in cultured primary renal interstitial fibroblasts than those of Insig1flox/flox mice (Fig. 4A–C).