Urocortin II gene is highly expressed in mouse skin and skeletal muscle tissues: Localization, basal expression in corticotropin-releasing factor receptor (CRFR) 1-and CRFR2-null mice, and regulation by glucocorticoids
Urocortin II gene is highly expressed in mouse skin and skeletal muscle tissues: Localization, basal expression in corticotropin-releasing factor receptor (CRFR) 1-and CRFR2-null mice, and regulation by glucocorticoids
复制标题
DOI：
10.1210/en.2003-1570
复制
发表时间：
2004-05-01
期刊：
影响因子：
4.8
通讯作者：
Vale, W
中科院分区：
文献类型：
--
作者：
Chen, A;Blount, A;Vale, W
由尿皮质素 (Ucn) II 基因编码的肽，也称为应激素相关肽，最近被鉴定为促肾上腺皮质激素释放因子 (CRF) 家族的新成员。 Ucn II 是 2 型 CRF 受体 (CRFR) 的特异性配体。我们通过使用特定的 mUcn II 核糖核酸酶保护测定、RT-PCR、Southern 杂交和 DNA 测序，证明了小鼠 Ucn (mUcn) II 转录物的外周分布。尽管 Ucn II mRNA 在多种外周组织中广泛表达，但我们发现它在皮肤和骨骼肌组织中表达最高。使用 mUcn II 的特定 RIA，我们在小鼠大脑、肌肉和皮肤的酸提取物中检测到 Ucn II 样免疫反应性 (ir)。免疫组织化学研究揭示了皮肤表皮和附件结构以及骨骼肌肌细胞中存在 Ucn II 样 ir。 Ucn II mRNA 和 ir 也在新生儿骨骼肌培养物中观察到，其中 Ucn II 定位于肌管。我们发现，与野生型同窝小鼠相比，CRFR1 缺失小鼠和 CRFR2 缺失小鼠皮肤中的 Ucn II mRNA 水平显着增加，但骨骼肌中的 Ucn II mRNA 水平没有显着增加。我们发现，给小鼠注射地塞米松后，腹腔注射 12 小时后，小鼠背部皮肤区域的 Ucn II mRNA 水平下降。切除肾上腺后，皮肤中 Ucn II mRNA 的水平显着增加，而皮质酮替代后，该水平又降至正常水平。进一步检查 CRFR2 及其特异性配体 Ucn II 在皮肤和骨骼肌组织中的分布和调节可能会揭示 CRFR2 通路参与这些组织中应激的生理反应以及皮肤和肌肉的其他病理生理学的方式。
Peptides encoded by the Urocortin (Ucn) II gene, also known as stresscopin-related peptide, were recently identified as new members of the corticotropin-releasing factor (CRF) family. Ucn II is a specific ligand for the type 2 CRF receptor (CRFR). We have demonstrated the peripheral distribution of mouse Ucn (mUcn) II transcripts by using specific mUcn II ribonuclease protection assays, RT-PCR, Southern hybridization, and DNA sequencing. Although Ucn II mRNA is widely expressed in a variety of peripheral tissues, we found it to be most highly expressed in the skin and skeletal muscle tissues. Using a specific RIA for mUcn II, we detected Ucn II-like immunoreactivity (ir) in acid extracts of mouse brain, muscle, and skin. Immunohistochemical studies revealed Ucn II-like ir in both skin epidermis and adnexal structures and in the skeletal muscle myocytes. Ucn II mRNA and ir were also observed in neonatal skeletal muscle cultures in which Ucn II was localized to the myotube. We found a significant increase in Ucn II mRNA levels in the skin, but not in skeletal muscle, of both CRFR1- and CRFR2-null mice compared with their wild-type littermates. We showed that administration of dexamethasone to mice resulted in a decrease of Ucn II mRNA levels in the back skin region 12 h after ip injections. Removal of the adrenal gland significantly increased the levels of Ucn II mRNA in the skin, and the levels were reduced back to normal levels after corticosterone replacement. Further examination of the distribution and regulation of CRFR2 and its specific ligand Ucn II in the skin and skeletal muscle tissues may reveal the manner by which the CRFR2 pathway is involved in the physiological responses to stress in these tissues and in other pathophysiologies of the skin and muscle.