Pulmonary fibrosis is a fatal lung disease affecting approximately 5 million people worldwide, with a 5-year survival rate of less than 50%. Currently, the only available treatments are palliative care and lung transplantation, as there is no curative drug for this condition. The disease involves the excessive synthesis of the extracellular matrix (ECM) due to alveolar epithelial cell damage, leading to scarring and stiffening of the lung tissue and ultimately causing respiratory failure. Although multiple factors contribute to the disease, the exact causes remain unclear. The mechanical properties of lung tissue, including elasticity, viscoelasticity, and surface tension, are not only affected by fibrosis but also contribute to its progression. This paper reviews the alteration in these mechanical properties as pulmonary fibrosis progresses and how cells in the lung, including alveolar epithelial cells, fibroblasts, and macrophages, respond to these changes, contributing to disease exacerbation. Furthermore, it highlights the importance of developing advanced in vitro models, based on hydrogels and 3D bioprinting, which can accurately replicate the mechanical and structural properties of fibrotic lungs and are conducive to studying the effects of mechanical stimuli on cellular responses. This review aims to summarize the current understanding of the interaction between the progression of pulmonary fibrosis and the alterations in mechanical properties, which could aid in the development of novel therapeutic strategies for the disease.

Necroptosis of intestinal epithelial cells has been indicated to play an important role in the pathogenesis of inflammatory bowel disease (IBD). The identification of dysregulated proteins that can regulate necroptosis in dextran sulfate sodium (DSS)-induced colitis is the key to the rational design of therapeutic strategies for colitis. Through Tandem Mass Tag (TMT)-based quantitative proteomics, HtrA2 was found to be downregulated in the colon of DSS-treated mice. UCF-101, a specific serine protease inhibitor of HtrA2, significantly alleviated DSS-induced colitis as indicated by prevention of body weight loss and decreased mortality. UCF-101 decreased DSS-induced colonic inflammation, prevented intestinal barrier function loss and inhibited necroptosis of intestinal epithelial cells. In vitro , UCF-101 or silencing of HtrA2 decreased necroptosis of HT-29 and L929 cells. UCF-101 decreased phosphorylation of RIPK1 and subsequent phosphorylation of RIPK3 and MLKL during necroptosis. HtrA2 directly interacted with RIPK1 and promoted its degradation during a specific time phase of necroptosis. Our findings highlight the importance of HtrA2 in regulating colitis by modulation of necroptosis and suggest HtrA2 as an attractive target for anti-colitis treatment.