Role of secretoglobin 3A2 in lung development
Role of secretoglobin 3A2 in lung development
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DOI：
10.1164/rccm.200707-1104oc
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发表时间：
2008-08-15
影响因子：
24.7
通讯作者：
Kimura, Shioko
中科院分区：
文献类型：
--
作者：
Kurotani, Reiko;Tomita, Takeshi;Kimura, Shioko
原理：分泌型珠蛋白3A2(SCGB3A2)最初被认为是同源结构域转录因子NKX2-1在肺中的下游靶点，其零突变导致严重的肺发育不良。在小鼠胚胎发育的第11.5天，SCGB3A2在肺中的表达水平很低，到E16.5，即肺的形态发生剧烈变化的时候，表达水平显著增加，这表明SCGB3A2除了参与肺部炎症的已知作用外，还可能参与肺的发育。目的：为了确定SCGB3A2是否在肺发育中发挥作用。方法：对发育早期的野生型和Nkx2-1缺失的胎肺进行体外器官培养。Nkx2-1缺失型胎儿通过静脉注射SCGB3A2蛋白给携带Nkx2-1缺失型胎儿的Nkx2-1杂合子妊娠女性暴露于器官发生早期。对培养的肺和胎肺进行组织学和免疫组织化学分析。为了评估SCGB3A2在肺发育后期的作用，在器官发生的中晚期，给怀孕的野生型雌性幼鼠注射SCGB3A2，通过呼吸运动、肺的大体形态和组织学、妊娠阶段特异基因的表达和磷脂谱来评估早产幼鼠和/或其肺的成熟程度。测量和主要结果：SCGB3A2对肺发育的早期和晚期都有明显的促进作用。
Rationale: Secretoglobin 3A2 (SCGB3A2) was originally identified as a downstream target in lung for the homeodomain transcription factor NKX2-1, whose null mutation resulted in severely hypoplastic lungs. A very low level of SCGB3A2 is expressed in lungs at Embryonic Day (E) 11.5 during mouse development, which markedly increases by E16.5, the time when lung undergoes dramatic morphologic changes, suggesting that SCGB3A2 may be involved in lung development in addition to a known role in lung inflammation.Objectives: To determine whether SCGB3A2 plays a role in lung development.Methods: To assess a potential role for SCGB3A2 during early lung development, wild-type and Nkx2-1-null fetal lungs of early developmental stages were subjected to ex vivo organ culture in the presence of SCGB3A2. Nkx2-1-null fetuses were exposed to SCGB3A2 during early organogenesis period through intravenous administration of this protein to Nkx2-1-heterozygous pregnant females carrying these null fetuses. Cultured lungs and fetal lungs were subjected to histologic and immunohistochemical analyses. To assess a role for SCGB3A2 in late lung development, SCGB3A2 was administered to pregnant wild-type females during mid- to late organogenesis stages, and the preterm pups and/or their lungs were evaluated for extent of maturity using breathing motion, gross morphology and histology of lungs, expression of gestational stage-specific genes, and phospholipid profiles.Measurements and Main Results: SCGB3A2 significantly promoted both early and late stages of lung development.Conclusions: SCGB3A2 is a novel growth factor in lung.