1D11 reversed pre-existing hepatic fibrosis.

<p><b>A</b>. Representative photomicrographs of picrosirius red stained liver sections following treatment with TAA for 8 weeks (“baseline”; TAA-8W), or an additional 8 weeks with 13C4 (13C4–16W) or 1D11 (1D11–16W) after cessation of TAA administration. A normal rat liver is also shown (Normal). Livers of rats dosed with TAA for 8 weeks (TAA-8W) had substantial lesions with widely spread fibrous bands (septa), originating from portal areas and extending into the parenchyma. 8 weeks after stopping TAA dosing, fibrotic areas were further expanded, with extensive architectural disorganization and more fibrosis covering a greater percentage of the livers (13C4–16W). Treatment with 1D11 for 8 weeks significantly ameliorated the TAA-mediated histopathological lesions, as shown by an overall improvement in hepatic morphology (1D11–16W). Liver collagen deposition in rats treated with 1D11 was noticeably much reduced than the pre-established fibrosis seen at baseline (TAA-W8), shown in rats that were examined at baseline. Magnification: 40x. <b>B</b>. Morphometric analysis of picrosirius red stained sections. Significantly less collagen was deposited in livers treated with 1D11 (▴) for 4 weeks or 8 weeks, when compared to the PBS (•, * p<0.01) or 13C4 (▪, * p<0.01) treatment groups. Moreover, comparison of 1D11 treated livers to those at week 8 before therapeutic treatment started, showed significantly less collagen deposition (treatment for 4 weeks: 9.61%; 8 weeks: 7.53%, * p<0.05) than that harvested at baseline (week 8∶12.7%). Morphometric quantification further supports the histology of a reversal of pre-existing hepatic fibrosis when TGF-β was neutralized by 1D11. Values represent the percentage of collagen deposition in the total liver section and are expressed as mean ± SE (n = 8, except n = 4 for normal controls at week 0).