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Inhalable siRNA Targeting IL-11 Nanoparticles Significantly Inhibit Bleomycin-Induced Pulmonary Fibrosis.
ACS Nano
January 2025
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
For idiopathic pulmonary fibrosis (IPF), interleukin 11 (IL-11) is a pivotal cytokine that stimulates the transformation of fibroblasts into myofibroblasts, thus accelerating the progression of pulmonary fibrosis. Here, we develop an innovative inhalable small interfering RNA (siRNA) delivery system termed PEI-GBZA, which demonstrates impressive efficiency in loading siIL-11 targeting IL-11 (siIL-11) and substantially suppresses the differentiation of fibroblasts into myofibroblasts and epithelial-mesenchymal transition (EMT), reduces neutrophil and macrophage recruitment, and ultimately relieves the established fibrotic lesions in the IPF model. PEI-GBZA is prepared by modifying low-molecular-weight polyethylenimine (PEI) with 4-guanidinobenzoic acid (GBZA).
View Article and Find Full Text PDFKlotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways.
Int J Mol Med
March 2025
Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Retinal pigment epithelial (RPE) cells undergoing epithelial‑mesenchymal transition (EMT) are a key factor in promoting the progression of subretinal fibrosis. The klotho protein and gene exert anti‑fibrotic effects in multiple fibrotic diseases. However, the mechanisms involved in the role of klotho are unclear in subretinal fibrosis.
View Article and Find Full Text PDFLOX-induced tubulointerstitial fibrosis via the TGF-β/LOX/Snail axis in diabetic mice.
J Transl Med
January 2025
Department of Basic Medical Sciences, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
Background: The partial epithelial-mesenchymal transition (EMT) is emerging as a significant mechanism in diabetic nephropathy (DN). LOX is a copper amine oxidase conventionally thought to act by crosslinking collagen. However, the role of LOX in partial EMT and fibrotic progression in diabetic nephropathy has not been investigated experimentally.
View Article and Find Full Text PDFAlleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells.
Nat Commun
January 2025
Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions.
View Article and Find Full Text PDFRecombinant Thrombomodulin Domain 1 Modulates Macrophage Polarization and Enhances Healing in Corneal Alkali Burns.
Invest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Purpose: Corneal alkali burns are severe ocular injuries characterized by intense inflammation, tissue damage, and vision impairment, with current treatments often insufficient in restoring corneal function and clarity. This study aimed to evaluate the therapeutic effects of recombinant thrombomodulin domain 1 (rTMD1) in the treatment of corneal alkali burns, focusing on its impact on inflammation, tissue repair, fibrosis, and neovascularization.
Methods: A murine model of corneal alkali burn was utilized to investigate the therapeutic potential of rTMD1.
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