Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation
Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation
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DOI：
10.1203/pdr.0b013e3180332c8d
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发表时间：
2007-04-01
影响因子：
3.6
通讯作者：
Guarino, Alfredo
中科院分区：
文献类型：
--
作者：
Buccigrossi, Vittoria;De Marco, Giulio;Guarino, Alfredo
人乳通过各种成分的作用刺激肠道发育。乳铁蛋白（LF）是人乳中的一种糖蛋白，其浓度在初乳中最高，在成熟乳中逐渐降低。LF促进肠细胞系中肠细胞的生长。我们测试的假设，LF诱导肠上皮细胞增殖和分化的不同效果，这取决于其浓度。我们在Caco-2（人结肠腺癌）细胞中检测了人天然LF（N-LF）的剂量相关效应。在高浓度下，N-LF刺激未成熟Caco-2细胞的细胞增殖，H-3-胸苷掺入判断。与此相反，蔗糖酶和乳糖酶的活性增加，但不高LF浓度和它们的mRNA也增加，表明转录的影响。由于铁结合特定的LF位点，我们比较了N-LF和铁饱和LF（I-LF）的效力，发现天然形式更有效。最后，我们测试了牛LF（bLF）在同一系统中的作用，发现后者在诱导细胞生长和乳糖酶表达方面比人的同种型更有效。这些结果表明，LF直接诱导肠上皮细胞的生长和增殖，这取决于其浓度，从而调节早期和出生后肠道发育。bLF可用于婴儿。配方作为生长因子在选定的肠道疾病。
Human milk stimulates intestinal development through the effects of various moieties. Lactoferrin (LF) is a glycoprotein of human milk whose concentration is highest in colostrum decreasing in mature milk. LF promotes enterocyte growth in intestinal cell lines. We tested the hypothesis that LF induces a distinct effect on enterocyte proliferation and differentiation, depending on its concentration. We examined the dose-related effects by human-native LF (N-LF) in Caco-2 (human colon adenocarcinoma) cells. At high concentrations, N-LF stimulated cell proliferation in immature Caco-2 cells, as judged by H-3-thymidine incorporation. In contrast, sucrase and lactase activities were increased at low but not high LF concentrations and their mRNA were also increased, indicating a transcriptional effect. Because iron binds specific LF sites, we compared the potency of N-LF and iron-saturated LF (I-LF) and found the native form more potent. Finally, we tested the effects by bovine LF (bLF) in the same system and found the latter more potent than the human isoform in inducing cell growth and lactase expression. These results suggest that LF directly induces enterocyte growth and proliferation, depending on its concentration, thereby regulating the earlyx postnatal intestinal development. bLF could be added to infant. formula as a growth factor in selected intestinal diseases.