Increased Levels of ER Stress and Apoptosis in a Sheep Model for Pulmonary Fibrosis Are Alleviated by In Vivo Blockade of the KCa3.1 Ion Channel

Figure 3

The effects of senicapoc and pirfenidone on ER stress induced by bleomycin in type II AECs and macrophages. (a) In individual sheep, the left caudal lung segment received infusions of bleomycin, while the right caudal lung segment received the saline. (b) Diagram shows the timeline of the bleomycin administration, treatment protocols (methylcellulose (control), senicapoc, pirfenidone) of the three groups of sheep, and the tissue collection. (c) Representative images from immunohistochemical staining against GRP78 to identify ER stress in type II AECs and macrophages in sheep lung segments treated with either methylcellulose (control), senicapoc, or pirfenidone. Arrows indicate ER stressed type II alveolar epithelial cells (AECs) and macrophages (M). (d, e) Graphs show the rate of ER stress in type II AECs and macrophages between the different treatment groups (n = 10 sheep/group). The data was collected from twenty representative, non-overlapping fields captured at 40x magnification. Each bar represents the mean ± standard error of the mean. Significance was determined by one-way ANOVA and a Tukey’s post hoc test to make multiple comparisons test between groups. , , and .

(a)

(b)

(c)

(d)

(e)