Objective: To explore the role of connective tissue growth factor (CTGF) on pulmonary artery remodeling induced by smoke exposure in rats.
Methods: Thirty-five male Wistar rats were randomly assigned into a control group (A group), a smoke exposure one month group (B group), a smoke exposure and high dose CTGF antisense oligonucleotide (ASON) one month group (C group), a smoke exposure and low dose CTGF ASON one month group (D group), a smoke exposure two month group (E group), a smoke exposure and high dose CTGF ASON two month group (F group), and a smoke exposure and low dose CTGF ASON two month group (G group). Pulmonary artery remodeling was observed by hematoxylin-eosin staining, and the CTGF mRNA expressions of pulmonary arteries were evaluated by RT-PCR. Immunohistochemistry methods were performed to determine CTGF protein expression in pulmonary artery smooth muscle. The difference between the groups was analyzed.
Results: (1) The pulmonary artery WA% of the seven groups were respectively (28.6 +/- 1.2)%, (42.5 +/- 2.3)%, (33.7 +/- 1.8)%, (42.1 +/- 2.4)%, (49.6 +/- 2.1)%, (34.3 +/- 1.9)% and (38.4 +/- 2.0)%. There was significant difference between B group and C group (q = 5.09, P < 0.01). Compared to E group, there were significant decreases in F group and G group (q = 8.15, 3.75, all P < 0.05). (2) The CTGF protein expressions (A value) of pulmonary artery smooth muscle were respectively 0.098 +/- 0.015, 0.159 +/- 0.023, 0.118 +/- 0.017, 0.153 +/- 0.022, 0.406 +/- 0.036, 0.109 +/- 0.012 and 0.146 +/- 0.024. There was significant difference between B group and C group (q = 3.26, P < 0.05). Compared to E group, there were significant decreases in F group and G group (q = 67.08, 18.09, all P < 0.01). (3) The CTGF mRNA expressions (A(CTGF)/A(beta-actin)) of pulmonary artery were respectively 0.051 +/- 0.010, 0.823 +/- 0.096, 0.216 +/- 0.056, 0.810 +/- 0.085, 2.452 +/- 0.267, 0.207 +/- 0.062 and 0.509 +/- 0.067. There was significant difference between B group and C group (q = 53.50, P < 0.01). Compared to E group, there were significant decreases in F group and G group (q = 132.22, 93.70, all P < 0.01).
Conclusion: Administration of CTGF ASON in vivo could significantly reduce pulmonary artery remodeling induced by smoke exposure in rats, indicating that CTGF may play an important role in pulmonary hypertension.