{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeuronal regeneration‐related protein (NREP, also known as P311) is a small, intrinsically disordered RNA‐binding protein that plays a pivotal role in regulating transforming growth factor–β (TGF‑β) isoform translation and mediating fibrogenic responses. In diverse tissues, forced NREP expression prompts a myofibroblastic transformation characterized by the upregulation of smooth muscle actin, collagen deposition, and growth factor release, while in some contexts it can simultaneously inhibit components of the TGF‑β signaling cascade. Mechanistically, NREP interacts with translation initiation factors such as eIF3b and directly binds TGF‑β mRNA 5′‑UTRs to stimulate isoform translation—a process critical for proper scar formation, renal fibrosis, and pulmonary fibrogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fibrogenic actions, NREP exerts a strong influence on cellular motility and tissue repair. It promotes cell migration in several settings—for example, by enhancing epidermal stem cell mobility via RhoA and Rac1 activation to accelerate reepithelialization during wound healing, and by modulating actin dynamics in glioma cells through interactions with filamin A and β1 integrin signaling. NREP also drives epithelial-to-mesenchymal transition in skin, contributing to scar remodeling, and impacts macrophage polarization during the inflammatory-to-healing transition. Emerging evidence additionally links NREP expression to lung and non–small cell lung cancer biology as well as its binding with other intracellular mediators in fibroblasts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, NREP expression is developmentally and contextually regulated. Its peak expression coincides with critical periods of lung alveolar formation, and diminished levels have been associated with impaired alveolar regeneration in emphysematous lungs. In the liver, NREP insufficiency leads to extensive transcriptomic remodeling—altering lipid metabolism, phosphatidylinositol signaling, and calcium flux—that contributes to the pathogenesis of nonalcoholic fatty liver disease. Epigenetic modifications, including m6A methylation and histone lactylation, further modulate NREP expression in pulmonary fibrosis driven by environmental insults. Collectively, these findings position NREP as an integrative modulator linking translational control, cell differentiation, and metabolic regulation in both physiological development and pathologic remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Desi Pan, Xiaoning Zhe, Sandhya Jakkaraju, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "P311 promotes renal fibrosis via TGFβ1/Smad signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep17032"}], "href": "https://doi.org/10.1038/srep17032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26616407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26616407"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Michael M Yue, Kaosheng Lv, Stephen C Meredith, et al. 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