| First Author | Oruqaj G | Year | 2023 |
| Journal | Am J Pathol | Volume | 193 |
| Issue | 3 | Pages | 259-274 |
| PubMed ID | 36521562 | Mgi Jnum | J:339214 |
| Mgi Id | MGI:7446054 | Doi | 10.1016/j.ajpath.2022.11.006 |
| Citation | Oruqaj G, et al. (2023) Transforming Growth Factor-beta1 Regulates Peroxisomal Genes/Proteins via Smad Signaling in Idiopathic Pulmonary Fibrosis Fibroblasts and Transgenic Mouse Models. Am J Pathol 193(3):259-274 |
| abstractText | Idiopathic pulmonary fibrosis (IPF) is a chronic human disease with persistent destruction of lung parenchyma. Transforming growth factor-beta1 (TGF-beta1) signaling plays a pivotal role in the initiation and pathogenesis of IPF. As shown herein, TGF-beta1 signaling down-regulated not only peroxisome biogenesis but also the metabolism of these organelles in human IPF fibroblasts. In vitro cell culture observations in human fibroblasts and human lung tissue indicated that peroxisomal biogenesis and metabolic proteins were significantly down-regulated in the lung of 1-month-old transgenic mice expressing a constitutively active TGF-beta type I receptor kinase (ALK5). The peroxisome biogenesis protein peroxisomal membrane protein Pex13p (PEX13p) as well as the peroxisomal lipid metabolic enzyme peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) and antioxidative enzyme catalase were highly up-regulated in TGF-beta type II receptor and Smad3 knockout mice. This study reports a novel mechanism of peroxisome biogenesis and metabolic regulation via TGF-beta1-Smad signaling: interaction of the Smad3 transcription factor with the PEX13 gene in chromatin immunoprecipitation-on-chip assay as well as in a bleomycin-induced pulmonary fibrosis model applied to TGF-beta type II receptor knockout mice. Taken together, data from this study suggest that TGF-beta1 participates in regulation of peroxisomal biogenesis and metabolism via Smad-dependent signaling, opening up novel strategies for the development of therapeutic approaches to inhibit progression of pulmonary fibrosis patients with IPF. |
