Problem: Intrauterine adhesion (IUA) is a uterine disorder with partial or total obstruction of the uterine cavity and/or the cervical canal primarily caused by intrauterine operations and infections. It is the most common cause of uterine infertility and recurrent abortion. However, the reasons for endometrium repair disorders in patients with IUA are still unclear. While increasing evidence demonstrates that endometrial mesenchymal stem/stromal cells (EMSCs) contribute to the regeneration and repair of endometrium, the roles of EMSCs in the pathogenesis of IUA have not been reported. Methods and study:We investigated the differences of phenotype and biological characteristics between EMSCs from women with IUA and healthy women. Firstly, the fibrosis of endometrium were measured by immunohistochemistry and Masson staining. Second, we used immunofluorescence to detect the location of EMSCs in endometrial tissue, and the proportion of CD146 + CD140b + in the two groups was compared by flow cytometry. Then, plate colony formation experiment, CCK-8 assay, flow cytometry, would-healing assay, and transwell invasion experiment were used to compare the cloning ability, proliferation, cell cycle, migration and invasion capabilities respectively. Finally, we compared the potential angiogenesis and immunosuppression capabilities.Results: Our results showed that there were fewer CD146 + CD140b + cells in patients with IUA, and the clone-forming, migration, invasion, angiogenic and immunosuppressive abilities of the EMSCs of patients with IUA were significantly decreased compared with those of healthy women. Conclusion:There are some differences between the EMSCs of IUA patients and healthy women, which may be related to the occurrence of IUA and dysfunction of endometrium.

Pulmonary fibrosis (PF) is a chronic, progressive, fatal interstitial lung disease with limited available therapeutic strategies. We recently reported that the protein kinase glycogen synthase kinase-3 β (GSK-3 β ) interacts with and inactivates the ubiquitin-editing enzyme A20 to suppress the degradation of the transcription factor CCAAT/enhancer-binding protein beta (C/EBP β ) in alveolar macrophages (AMs), resulting in a profibrotic phenotype of AMs and promoting the development of PF. Here, we showed that chronic lung injury upregulated the stress response protein tribbles homolog 3 (TRIB3), which interacted with GSK-3 β and stabilized GSK-3 β from ubiquitination and degradation. Elevated GSK-3 β expression phosphorylated A20 to inhibit its ubiquitin-editing activity, causing the accumulation of C/EBP β and the production of several profibrotic factors in AMs and promoting PF development. Activated C/EBP β , in turn, increased the transcription of TRIB3 and GSK-3 β , thereby establishing a positive feedback loop in AMs. The knockdown of TRIB3 expression or the pharmacologic disruption of the TRIB3‒GSK-3 β interaction was an effective PF treatment. Our study reveals an intact profibrotic axis of TRIB3‒GSK-3 β ‒A20‒C/EBP β in AMs, which represents a target that may provide a promising treatment strategy for PF.

Idiopathic pulmonary fibrosis (IPF), characterized by progressive worsening of dyspnea and irreversible decline in lung function, is a chronic and progressive respiratory disease with a poor prognosis. Chronic or repeated lung injury results in inflammation and an excessive injury-repairing response that drives the development of IPF. A number of studies have shown that the development and progression of IPF are associated with dysregulated expression of several chemokines and chemokine receptors, several of which have been used as predictors of IPF outcome. Chemokines of the CC family play significant roles in exacerbating IPF progression by immune cell attraction or fibroblast activation. Modulating levels of detrimental CC chemokines and interrupting the corresponding transduction axis by neutralizing antibodies or antagonists are potential treatment options for IPF. Here, we review the roles of different CC chemokines in the pathogenesis of IPF, and their potential use as biomarkers or therapeutic targets.

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