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Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor-β signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses. Here, we determined whether Lefty A can attenuate bleomycin (BLM)-induced pulmonary fibrosis in vivo based on a novel therapeutic strategy where human embryonic kidney 293 (HEK293) cells are genetically engineered with the Lefty A-associated gene. The engineered HEK293 cells were encapsulated in alginate microcapsules and then subcutaneously implanted in ICR mice that had 1 wk earlier been intratracheally administered BLM to induce pulmonary fibrosis. The severity of fibrosis in lung tissue was assessed using pathological morphology and collagen expression to examine the effect of Lefty A released from the microencapsulated cells. The engineered HEK293 cells with Lefty A significantly reduced the expression of connective tissue growth factor and collagen type I mRNA, lessened the morphological fibrotic effects induced by BLM, and increased the expression of matrix metalloproteinase-9. This illustrates that engineered HEK293 cells with Lefty A can attenuate pulmonary fibrosis in vivo, thus providing a novel method to treat human pulmonary fibrotic disease and other organ fibroses.

BACKGROUNDFat replacers prepared from polysaccharides and proteins possess functional properties of both polysaccharides and proteins. In this study, an aqueous system of barley β‐glucan (BBG) and gluten was prepared. The interactions between BBG and gluten (with/without extrusion modification) were studied. Triple analysis methods, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and low‐field nuclear magnetic resonance (LF‐NMR), were utilized to analyze the freezing–thawing and thermal evaporation process, as well as the distribution state of water. Meanwhile, fluorescence microscopic analysis, dynamic rheological analysis and electrophoresis analysis were used to study the structure and rheological properties of the system.RESULTSThe results showed that BBG significantly increased the water‐holding capacity of gluten, regardless of extrusion treatment, with the water absorption reaching about 4.8 to 6.4 times of its weight, which was 1 to 2.5 times higher than that without BBG. The triple analysis results suggested that BBG increased the binding capacity of the system to weakly bound water, hindered the aggregation of gluten and reduced the thermal decomposition temperature of the BBG and gluten composite system. After the gluten was extruded and homogenized with the BBG solution, the appearance of the composite system was more uniform and delicate.CONCLUSIONSIn conclusion, BBG increased the water‐holding capacity of the BBG and gluten composite system. With these changes, the composite system presented great potential for the preparation of polysaccharide–gluten fat replacer. © 2023 Society of Chemical Industry.