Fig. 8: Silencing of Prdx3 promotes pulmonary fibrosis in BLM-treated YAP1-cKI mice. | Experimental & Molecular Medicine

Fig. 8: Silencing of Prdx3 promotes pulmonary fibrosis in BLM-treated YAP1-cKI mice.

From: YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis

Fig. 8

a Schematic of the experimental design showing the silencing of Prdx3 in YAP1-cKI mice treated with BLM. b Pulmonary function parameters, including Cst and IC, were measured in YAP1-cKI mice treated with AAV5-sh-Prdx3 or AAV5-sh-NC; n = 4. c Micro-CT images of the axial plane (upper panels) and corresponding coronal plane (middle panels) in YAP1-cKI mice treated with AAV5-sh-Prdx3 or AAV5-sh-NC. The bottom panels show images of three-dimensional reconstructions of lung tissues based on the density; n = 3. d Western blot analysis of Fn1 and α-SMA protein expression in YAP1-cKI mice treated with AAV5-sh-Prdx3 or AAV5-sh-NC; n = 6. e The mRNA expression of Fn1, Collagen 1α1, Collagen 3α1, and ACTA2 in YAP1-cKI mice treated with AAV5-sh-Prdx3 or AAV5-sh-NC was measured by qRT–PCR; n = 5. f, g Images of Masson’s trichrome staining and immunohistochemical staining in paraffin-embedded lung sections from YAP1-cKI mice treated with AAV5-sh-Prdx3 or AAV5-sh-NC. Scale bars, 50 μm. h The hydroxyproline content was measured in YAP1-cKI mice treated with AAV5-sh-Prdx3 or AAV5-sh-NC; n = 6. i Images of HE staining in lung paraffin sections of YAP1-cKI mice treated with AAV5-sh-Prdx3 or AAV5-sh-NC. Scale bars, 50 μm. j SA-β-gal staining of frozen lung tissue sections from AAV5-sh-Prdx3- or AAV5-sh-NC-treated YAP1-cKI mice. Scale bars, 50 μm. k Western blot analysis of p21 protein expression in YAP1-cKI mice treated with AAV5-sh-Prdx3 or AAV5-sh-NC; n = 6. l Transmission electron microscopy images of tissue samples from YAP1-cKI mice intratracheally injected with AAV5-sh-Prdx3 or AAV5-sh-NC. Scale bars, 500 nm. m Western blot analysis of the protein expression of Drp1 and Mfn2 in YAP1-cKI mice intratracheally injected with AAV5-sh-Prdx3 or AAV5-sh-NC; n = 6. n After exposure to injury stimuli, the expression of YAP1 in AT2 cells was significantly decreased, and YAP1 then lost its ability to bind to TEAD1 to upregulate Prdx3, an antioxidant enzyme in mitochondria. A decrease in Prdx3 expression led to ROS accumulation and mitochondrial dysfunction, which ultimately resulted in cellular senescence. Senescent AT2 cells secreted SASP factors to activate lung fibroblasts, which ultimately contributed to pulmonary fibrosis. This figure was generated by Figdraw. The data are presented as the means ± SEMs. *P < 0.05, **P < 0.01.

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