Pirfenidone Inhibits Hypoxic Pulmonary Hypertension through the NADPH/ROS/p38 Pathway in Adventitial Fibroblasts in the Pulmonary Artery

Figure 5

The PFD reduced the phosphorylation of p38 through the NOX4/ROS signaling pathway in HPAAFs exposed hypoxia. (a–d) Compared with normoxia, hypoxia increased the expression of NOX4 and ROS, while PFD reduced NOX4 protein expression and ROS expression in cultured HPAAFs (). (e, f) NOX4 expression was effectively interfered by shRNA or pcDNA3.1, and PFD significantly decreased the hypoxia-induced NOX4 expression (). (g, h) NOX4 inhibition or PFD significantly decreased the phosphorylation of p38 induced by hypoxia in HPAAFs, and overexpression of NOX4 by pcDNA3.1 increased the expression of p-p38 (). Nor: normoxia; Hyp: hypoxia; PFD: pirfenidone; p-p38: phosphorylated p38; t-p38: total p38; HPAAFs: human pulmonary arterial adventitial fibroblasts.

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