Lipocalin 2 functions as a negative regulator of red blood cell production in an autocrine fashion
Lipocalin 2 functions as a negative regulator of red blood cell production in an autocrine fashion
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DOI：
10.1096/fj.05-3809fje
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发表时间：
2005-09-01
期刊：
影响因子：
4.8
通讯作者：
Nakamura, Y
中科院分区：
文献类型：
--
作者：
Miharada, K;Hiroyama, T;Nakamura, Y
脂质运载蛋白家族的成员通常是具有多种功能的小型分泌蛋白。尽管脂质运载蛋白 2 的生理作用仍有待完全阐明，但最近报道了一些关键功能，例如。 g.，白细胞凋亡的调节。出乎意料的是，脂质运载蛋白 2 在红系祖细胞中大量表达。体外培养实验表明，lipocalin 2 可诱导细胞凋亡并抑制红系祖细胞的分化。急性贫血期间，红细胞中脂质运载蛋白 2 的表达通过反馈系统降低。此外，将重组脂质运载蛋白2注射到患有急性贫血的小鼠中会延迟红细胞(RBC)数量的恢复，这表明减少脂质运载蛋白2的表达对于有效恢复红细胞数量的重要性。这些结果表明脂质运载蛋白 2 以自分泌方式抑制红细胞产生。因此，病理状况（例如慢性炎症）引起的贫血可能部分是由于扩张的白细胞和/或巨噬细胞分泌的脂质运载蛋白2水平增加所致。此外，恶性肿瘤引起的贫血可能部分是由于肿瘤细胞大量分泌脂质运载蛋白 2。因此，脂质运载蛋白2可能代表某些病理条件下贫血症的有吸引力的治疗靶点。
Members of the lipocalin protein family are typically small, secreted proteins that possess a variety of functions. Although the physiological role of lipocalin 2 remains to be fully elucidated, a few pivotal functions have recently been reported, e. g., regulation of the apoptosis of leukocytes. Unexpectedly, lipocalin 2 is abundantly expressed in erythroid progenitor cells. An in vitro culture experiment demonstrated that lipocalin 2 induces apoptosis and inhibits differentiation of erythroid progenitor cells. During acute anemia the expression of lipocalin 2 was reduced in erythroid cells by a feedback system. Furthermore, injection of recombinant lipocalin 2 into mice suffering from acute anemia retarded the recovery of red blood cell (RBC) numbers, suggesting the importance of reduced expression of lipocalin 2 for the efficient recovery of RBC numbers. These results indicate that lipocalin 2 suppresses RBC production in an autocrine fashion. Hence, anemia arising from pathological conditions, such as chronic inflammation, might be partly due to increased levels of lipocalin 2 secreted from expanded leukocytes and/or macrophages. Also, anemia arising from malignancies might be partly due to the abundant secretion of lipocalin 2 from tumor cells. Thus, lipocalin 2 may represent an attractive therapeutic target for anemia under certain pathological conditions.