Adenosine A2A receptor blockade or deletion diminishes fibrocyte accumulation in the skin in a murine model of scleroderma, bleomycin-induced fibrosis.
Adenosine A2A receptor blockade or deletion diminishes fibrocyte accumulation in the skin in a murine model of scleroderma, bleomycin-induced fibrosis.
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DOI：
10.1007/s10753-008-9078-y
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发表时间：
2008-10
期刊：
影响因子：
5.1
通讯作者：
Cronstein, Bruce N.
中科院分区：
文献类型：
--
作者：
Katebi, Majid;Fernandez, Patricia;Chan, Edwin S. L.;Cronstein, Bruce N.
外周血纤维细胞是新鉴定的循环白细胞亚群，其迁移到损伤组织中，在损伤组织中其可显示成纤维细胞样性质并参与皮肤和其他器官的伤口愈合和纤维化。我们实验室先前的研究表明，A2A受体缺陷和A2A拮抗剂治疗的小鼠被保护免于发生博来霉素诱导的真皮纤维化，因此本研究的目的是确定腺苷A2A受体是否调节在博来霉素诱导的真皮纤维化模型中纤维细胞向真皮的募集。对正常小鼠和博来霉素处理的野生型、A2A敲除和A2A拮抗剂处理的小鼠的皮肤切片进行前胶原α2 I型和CD 34染色，并对组织切片中的双染色细胞、纤维细胞进行计数。博来霉素处理的小鼠真皮中的纤维细胞比正常小鼠多，并且通过缺失或阻断腺苷A2A受体来消除这种增加。由于纤维细胞在组织纤维化中起核心作用，这些结果表明，腺苷A2A受体介导的纤维细胞向组织中的募集减少可能在皮肤纤维化疾病的发病机制中起作用。此外，这些结果提供了进一步的证据，腺苷A2A受体可能代表一个新的目标，用于治疗这样的纤维化疾病，如硬皮病或肾源性纤维化皮肤病。
Peripheral blood fibrocytes are a newly identified circulating leukocyte subpopulation that migrates into injured tissue where it may display fibroblast-like properties and participate in wound healing and fibrosis of skin and other organs. Previous studies in our lab demonstrated that A2A receptor-deficient and A2A antagonist-treated mice were protected from developing bleomycin-induced dermal fibrosis, thus the aim of this study was to determine whether the adenosine A2A receptor regulates recruitment of fibrocytes to the dermis in this bleomycin-induced model of dermal fibrosis. Sections of skin from normal mice and bleomycin-treated wild type, A2A knockout and A2A antagonist-treated mice were stained for Procollagen α2 Type I and CD34 and the double stained cells, fibrocytes, were counted in the tissue sections. There were more fibrocytes in the dermis of bleomycin-treated mice than normal mice and the increase was abrogated by deletion or blockade of adenosine A2A receptors. Because fibrocytes play a central role in tissue fibrosis these results suggest that diminished adenosine A2A receptor-mediated recruitment of fibrocytes into tissue may play a role in the pathogenesis of fibrosing diseases of the skin. Moreover, these results provide further evidence that adenosine A2A receptors may represent a new target for the treatment of such fibrosing diseases as scleroderma or nephrogenic fibrosing dermopathy.
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影响因子：
7.3
作者：
Chan, Edwin S. L.;Montesinos, Maria Carmen;Cronstein, Bruce N.
通讯作者：
Cronstein, Bruce N.
影响因子：
15.9
作者：
Blackburn, MR;Lee, CG;Elias, JA
通讯作者：
Elias, JA
影响因子：
5
作者：
Quan, Timothy E;Cowper, Shawn E;Bucala, Richard
通讯作者：
Bucala, Richard
影响因子：
15.9
作者：
Phillips, RJ;Burdick, MD;Strieter, RM
通讯作者：
Strieter, RM
影响因子：
3.6
作者：
Desai, A;Victor-Vega, C;Cronstein, BN
通讯作者：
Cronstein, BN