| First Author | Nishio T | Year | 2021 |
| Journal | Proc Natl Acad Sci U S A | Volume | 118 |
| Issue | 29 | PubMed ID | 34253615 |
| Mgi Jnum | J:320457 | Mgi Id | MGI:6727162 |
| Doi | 10.1073/pnas.2101270118 | Citation | Nishio T, et al. (2021) Immunotherapy-based targeting of MSLN(+) activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis. Proc Natl Acad Sci U S A 118(29):e2101270118 |
| abstractText | We investigated the role of mesothelin (Msln) and thymocyte differentiation antigen 1 (Thy1) in the activation of fibroblasts across multiple organs and demonstrated that Msln(-/-) mice are protected from cholestatic fibrosis caused by Mdr2 (multidrug resistance gene 2) deficiency, bleomycin-induced lung fibrosis, and UUO (unilateral urinary obstruction)-induced kidney fibrosis. On the contrary, Thy1(-/-) mice are more susceptible to fibrosis, suggesting that a Msln-Thy1 signaling complex is critical for tissue fibroblast activation. A similar mechanism was observed in human activated portal fibroblasts (aPFs). Targeting of human MSLN(+) aPFs with two anti-MSLN immunotoxins killed fibroblasts engineered to express human mesothelin and reduced collagen deposition in livers of bile duct ligation (BDL)-injured mice. We provide evidence that antimesothelin-based therapy may be a strategy for treatment of parenchymal organ fibrosis. |
