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. 2023 Sep 13;24(18):14019. doi: 10.3390/ijms241814019

Figure 2.

Figure 2

TGF-β1 and Wnt/β-catenin activation in tubular damage. ROS, acids and plasmin can induce TGF-β1 detachment from LTBP and LAP. TGF-β1 induces phosphorylation to the SMAD2/3 complex, which is translocated into the nucleus by SMAD4 and exerts pro-fibrotic transcription genes through different miRNAs. The right part of the picture represents the Wnt/β-catenin pathway. Wnt ligands bind to FZD and LPR5/6, which will induce the inactivation of the “destruction complex”, leaving β-catenin unphosphorylated. Unphosphorylated β-catenin can translocate into the nucleus, bind to TCF/LEF and, subsequently, induce Wnt-dependent pro-fibrotic gene expression. Acronyms: ECM—extracellular matrix; FZD—Frizzled receptor; LAP—latency-associated peptide; LRP5/6—lipoprotein receptor-related protein 5/6; LTBP—latent TGF-β1 binding protein; miR—micro ribonucleic acid; MMP-7—matrix metalloproteinase-7; PAI-1—plasmin activator inhibitor-1; RAS—renin-angiotensin system; ROS—reactive oxygen species; SMAD—acronym for the Caenorhabditis elegans SMA, “small” worm phenotype and MAD family, “mothers against decapentaplegic” of genes in Drosophila; Snail—gene encoded a nuclear protein similar to Drosophila embryonic protein snail; TCF/LEF—T cell factor/lymphoid enhancer factor; TGF-β—transforming growth factor beta; TRPC6—transient receptor potential canonical 6; Wnt—wingless.