We hypothesized that short duration of mechanical stretch augmented diaphragmatic damage, and production of TGF-b1 via lumican pathway. In high tidal volume ventilation-induced diaphragmatic injury model in mice, we examined the relationships between different tidal volume of mechanical ventilation, TGF-b1-inducible genes, and TGF-b1 production using the lumican deficient mice. Recent studies suggested that increased inflammatory cytokines, extracellular matrix, and collagen formation might occur in the first week of ARDS, which caused reduced pulmonary compliance and severe hypoxemia. Identification of the mechanisms regulating fibrogenesis of ARDS will help development of better treatment regimens for diaphragmatic and lung injury in ARDS patients. In this injurious mechanical ventilation model of mouse, we found that high tidal volume ventilation increased interfibillar spacings and disruptions of diaphragmatic collagen, production of TGF-b1, TGF-b1-indubible genes, and free radical. Our hypothesis is lumican pathway was regulated by TGF-ß expression in the diaphragmatic injury. Previous studies have shown that patients experienced difficulty in weaning from prolonged mechanical ventilation may be linked to diaphragm dysfunction due to abnormal fiber remodeling resulting from oxidative stress, and repair of structural injury. The onset of VIDD is rapid within 6 hours after the initiation of mechanical ventilation and the magnitude of impairment of diaphragmatic contraction increased with time on the ventilator. We found that interfibrillar disassembly of diaphragmatic collagen fiber and oxidative injury after 8 hours of mechanical ventilation. We then explored the major physiologic trigger leading to these alterations. Collagen, as a supportive Ruxolitinib structure in skeletal muscle and tendon is the most abundant protein of the extracellular matrix. Mechanical ventilation for 2 to 5 hours in rats have been shown to increase the expression of type III procollagen, the first collagen type involved in the remodeling in the evolution of fibrogenesis and up-regulation of hyaluronan synthase 3 mRNA and HA production by fibroblasts, contributing to extracellular matrixinduced inflammatory changes involved in ventilator-induced lung injury. We found that mechanical ventilation increased expressions of mesenchymal markers, including type I and type III procollagen, fibronectin, and a-SMA mRNA in a timedependent manner. TGF-b1 is a multifunctional cytokine that plays an important role in the induction of extracellular matrix deposition by fibroblasts and may induce cytoskeletal reorganization found in epithelial-mesenchymal transition. Using human dermal fibroblasts, others showed that TGF-b1 increased the production of types I and III collagens and fibronectin but the chemotactic effects of TGFb1 have been shown to occur at concentrations much lower than those required for extracellular matrix induction in the lung. TGFb1 is no longer chemotactic at higher concentrations and may attract cells toward its source of delivery. As a major pro-fibrogenic cytokine, TGF-b1 was also found in the pathogenesis of acute lung injury related with mechanical ventilation.