Exosome-encapsulated lncRNA HOTAIRM1 contributes to PM2.5-aggravated COPD airway remodeling by enhancing myofibroblast differentiation.

Emphysema, myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution, especially fine particulate matter (PM2.5), leading to chronic obstructive pulmonary disease (COPD). Specifically, bronchial epithelium-fibroblast communication participates in airway remodeling, which results in COPD. An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis. Here, we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses, resulting in airway obstruction in COPD. We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial (HBE) cells and primary lung fibroblasts (pLFs). We found that PM2.5-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs. Then, the exosomal lncRNA expression profiles derived from PM2.5-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array. Combining coculture assays and direct exosome treatment, we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs. Surprisingly, we discovered that exosomal HOTAIRM1 enhanced pLF proliferation to secrete excessive collagen secretion, leading to airway obstruction by stimulating the TGF-ß/SMAD3 signaling pathway. Significantly, PM2.5 reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people; moreover, serum exosomal HOTAIRM1 was associated with PM2.5-related reductions in FEV1/FVC and FVC. These findings show that PM2.5 triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1, which has the potential to be an effective prevention and therapeutic target for PM2.5-induced COPD.

Effects of depression on healing and inflammatory responses of acute wounds in rats.

This study aimed to elucidate the effect of depression on the healing of acute wounds in rats. We hypothesized that depression would have negative effects on inflammation and wound healing and that antidepressant therapy would reverse these effects. This study included 100 rats randomly allocated into five groups: control group (CG), depression group (DG), pre-depression group (PDG), antidepressant group (AG), and pre-antidepressant group (PAG). Acute wounds were created on the rats' backs. The groups were subjected to no interventions (CG), aversive stimuli before (PDG) and after (DG) wound creation, and antidepressant treatment before (PAG) and after (AG) wound creation. On the day of wound creation and on days 3, 6, 9, and 12 after wound creation, observations of the wound area and degree of depression (evaluated using the sucrose preference test, open-field test, and weight change) were recorded. On days 6 and 12 after wound creation, venous serum and wound tissues were collected. Tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10 levels were measured using the enzyme-linked immunosorbent assay. Results showed an initial increase followed by a decrease in the degree of depression in all groups except DG (continuous decline). The wound-healing rate was significantly lower in PDG and DG than in CG; it was higher in AG and PAG than in CG. DG and PDG had higher concentrations of inflammatory cytokines than CG, and AG and PAG had lower concentrations than CG. This indicates that the onset of depression delays the healing of acute wounds and aggravates the inflammatory response in rats. Antidepressant treatment counteracts both of these negative effects.