Prostaglandin D2 Inhibits Collagen Secretion From Lung Fibroblasts by Activating the DP Receptor
Prostaglandin D2 Inhibits Collagen Secretion From Lung Fibroblasts by Activating the DP Receptor
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DOI：
10.1254/jphs.12275fp
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发表时间：
2013-04-01
影响因子：
3.5
通讯作者：
Murata, Takahisa
中科院分区：
文献类型：
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作者：
Ayabe, Shinya;Kida, Taiki;Murata, Takahisa
肺成纤维细胞负责正常组织修复和纤维化发展过程中的胶原蛋白分泌。据报道，许多其他的洋地黄素调节肺成纤维细胞中的胶原合成，但前列腺素D-2（PGD（2））的作用尚不清楚。在这项研究中，我们研究了PGD（2）对人肺成纤维细胞I型胶原分泌的影响。PGD预处理（2）（0.1-10 μ M，1小时）显著减弱转化生长因子-β诱导的I型胶原向细胞上清液的分泌（TGF-β）虽然对Th 2细胞上表达的化学引诱物受体同源分子（CRTH 2）的激动剂没有任何作用，前列腺素类DP受体激动剂BW 245 C（0.01 - 1 μ M）抑制TGF-β诱导的胶原蛋白分泌。PGD（2）和BW 245 C显著增加细胞内cAMP水平。毛喉素预处理一小时（0.1 - 10 μ M），二丁酰-cAMP（0.01 - 1 mM）和蛋白激酶A（PKA）-激活剂N-6-苯基-环AMP（100 μ M）显著降低TGF-β诱导的胶原蛋白分泌，而由cAMP（Epac）激活剂8-溴-2 ′-O-甲基腺苷-3 ′，5 '-环AMP（10 μ M）不影响胶原沉积。这些结果表明，PGD（2）通过激活DP受体，通过细胞内cAMP积累抑制TGF-β诱导的胶原分泌。
Lung fibroblasts are responsible for collagen secretion during normal tissue repair and the development of fibrosis. Many other prostaglandins have been reported to regulate collagen synthesis in lung fibroblasts, but the role of prostaglandin D-2 (PGD(2)) is unknown. In this study, we investigated the effect of PGD(2) on type I collagen secretion in human lung fibroblasts. Pretreatment with PGD(2) (0.1-10 mu M, 1 h) significantly attenuated type I collagen secretion to the cell supernatant induced by transforming growth factor-beta (TGF-beta) Although an agonist on chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) did not have any effect, the prostanoid DP-receptor agonist BW245C (0.01 - 1 mu M) suppressed TGF-beta-induced collagen secretion. PGD(2) and BW245C significantly increased intracellular cAMP level. One-hour pretreatment with forskolin (0.1 - 10 mu M), dibutyryl-cAMP (0.01 - 1 mM), and the protein kinase A (PKA)-activator N-6-phenyl-cyclic AMP (100 mu M) significantly reduced TGF-beta-induced collagen secretion, while exchange protein activated by cAMP (Epac) activator 8-bromo-2'-O-methyladenosine-3',5'-cyclic AMP (10 mu M) did not affect collagen deposition. These results suggest that PGD(2) inhibits TGF-beta-induced collagen secretion via intracellular cAMP accumulation through activating DP receptor.