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• W4310079400 abstract "Abstract Experimental autoimmune-orchitis (EAO), a rodent model of chronic testicular inflammation and fibrosis, replicates pathogenic changes seen in some cases of human spermatogenic disturbances. During EAO, increased levels of pro-inflammatory and pro-fibrotic mediators such as TNF, CCL2, and activin A are accompanied by infiltration of leukocytes into the testicular parenchyma. Activin A levels correlate with EAO severity, while elevated CCL2 acting through its receptor CCR2 mediates leukocyte trafficking and recruits macrophages. CCR2 + CXCR4 + macrophages producing extracellular matrix proteins contribute widely to fibrogenesis. Furthermore, testicular macrophages (TMs) play a critical role in organ homeostasis. Therefore, we aimed to investigate the role of the activin A/CCL2-CCR2/macrophage axis in the development of testicular fibrosis. Following EAO induction, we observed lower levels of organ damage, collagen deposition, and leukocyte infiltration (including fibronectin + , collagen I + and CXCR4 + TMs) in Ccr2 −/− mice than in WT mice. Furthermore, levels of Il-10 , Ccl2 , and the activin A subunit Inhba mRNAs were lower in Ccr2 −/− EAO testes. Notably, fibronectin + TMs were also present in biopsies from patients with impaired spermatogenesis and fibrotic alterations. Overexpression of the activin A antagonist follistatin reduced tissue damage and collagen I + TM accumulation in WT EAO testes, while treating macrophages with activin A in vitro increased the expression of Ccr2 , Fn1 , Cxcr4, and Mmp2 and enhanced migration along a CCL2 gradient; these effects were abolished by follistatin. Taken together, our data indicate that CCR2 and activin A promote fibrosis during testicular inflammation by regulating macrophage function. Inhibition of CCR2 or activin A protects against damage progression, offering a promising avenue for therapeutic intervention." @default.
• W4310079400 created "2022-11-30" @default.
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• W4310079400 date "2022-11-24" @default.
• W4310079400 modified "2023-10-10" @default.
• W4310079400 title "Activin A and CCR2 regulate macrophage function in testicular fibrosis caused by experimental autoimmune orchitis" @default.
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