Fig. 8
Loss of WT1 expression by PDGFRβ-expressing HSCs and myofibroblasts causes an enhanced fibrotic response to chronic injury without a change in myofibroblast number. a Chronic fibrosis was induced by iterative injury with CCl4 in animals in which WT1 had been constitutively deleted, or control animals. b The number of WT1-positive aHSCs after chronic injury in PDGFRβCre;WT1−/fl animals is significantly reduced compared with wild-type animals (295.8 ± 59.4 vs 829.8 ± 116.3 WT1-positive cells/10 pericentral fields, n = 6; Welch two-sample t-test, t(7.4397) = −4.0896, *p = 0.00407). Example pericentral fields from the livers of injured wild-type and WT1-deleted animals stained for WT1 and αSMA are shown. Scale bars 100 μm. c There is an enhanced fibrotic response to chronic injury in WT1-deleted PDGFRβCre;WT1−/fl animals (whole-slide PSR quantification of fibrotic matrix, 8.1 ± 0.6% vs 4.8 ± 0.5%, n = 6 (wild-type), n = 11 (PDGFRβCre;WT1−/fl); Welch two-sample t-test, t(13.765) = −4.194, *p = 0.0009388). Example PSR-stained sections of whole lobes of the livers of injured wild-type and WT1-deleted animals are shown. Scale bars 1 mm. d The enhanced fibrotic response to chronic injury in PDGFRβCre;WT1−/fl animals is not associated with increased numbers of aHSCs compared with wild-type animals (1007.8 ± 273.8 vs 927.0 ± 186.5 αSMA-positive cells/10 pericentral fields; Welch two-sample t-test, t(8.819) = −0.244), p = 0.8128). Data are represented as individual points with median (centre line), first and third quartiles (lower and upper box limits), 1.5× interquartile range (whiskers). e The use of PDGFRβCre;WT1GFP/fl animals allows continued GFP reporting to demonstrate the persistence of WT1-deleted aHSCs after pericentral chronic injury. Scale bars 100 μm
