The crosstalk between FGF21 and GH leads to weakened GH receptor signaling and IGF1 expression and is associated with growth failure in very preterm infants.
The crosstalk between FGF21 and GH leads to weakened GH receptor signaling and IGF1 expression and is associated with growth failure in very preterm infants.
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DOI：
10.3389/fendo.2023.1105602
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
成纤维细胞生长因子21（FGF 21）是一种重要的代谢调节因子，可适应营养状况的变化。严重的儿童期营养不良诱导升高的FGF 21水平，有助于生长激素（GH）抵抗和随后的线性生长衰减可能通过对软骨细胞的直接作用。在这项研究中，我们评估了生长激素和FGF 21途径在罕见和独特的人类生长板从儿童获得的组件的表达。此外，我们研究了在异源系统中FGF 21对GH受体（GHR）信号传导的机制相互作用。慢性FGF 21暴露增加GH诱导的GHR周转和SOCS 2表达，导致STAT 5磷酸化和IGF-1表达的抑制。通过GH受体的FGF 21信号传导的临床意义在出生后不久的极早产儿（VPT）中观察到的营养驱动的生长衰竭中进行了测试。VPT婴儿在出生后表现出立即的线性生长失败，随后是生长追赶。与体外模型数据一致，我们发现，与追赶生长相比，线性生长中的偏转期间循环FGF 21水平升高，并且与长度速度和循环IGF 1水平呈负相关。该研究进一步支持FGF 21在GH抗性和线性生长失败中的核心作用，并表明对生长板的直接作用。
Fibroblast growth factor 21 (FGF21) is an essential metabolic regulator that adapts to changes in nutritional status. Severe childhood undernutrition induces elevated FGF21 levels, contributing to growth hormone (GH) resistance and subsequent linear growth attenuation potentially through a direct action on chondrocytes. In this study, we assessed expression of the components of both GH and FGF21 pathways in rare and unique human growth plates obtained from children. Moreover, we investigated the mechanistic interplay of FGF21 on GH receptor (GHR) signaling in a heterologous system. Chronic FGF21 exposure increased GH-induced GHR turnover and SOCS2 expression, leading to the inhibition of STAT5 phosphorylation and IGF-1 expression. The clinical significance of FGF21 signaling through GH receptors was tested in nutritionally driven growth failure seen in very preterm (VPT) infants right after birth. VPT infants display an immediate linear growth failure after birth followed by growth catch-up. Consistent with the in vitro model data, we show that circulating FGF21 levels were elevated during deflection in linear growth compared to catch-up growth and were inversely correlated with the length velocity and circulating IGF1 levels. This study further supports a central role of FGF21 in GH resistance and linear growth failure and suggests a direct action on the growth plate.
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DOI：
10.1136/archdischild-2012-303536
发表时间：
2014-01
期刊：
Archives of disease in childhood. Fetal and neonatal edition
影响因子：
--
作者：
Cole TJ;Statnikov Y;Santhakumaran S;Pan H;Modi N;Neonatal Data Analysis Unit and the Preterm Growth Investigator Group
通讯作者：
Neonatal Data Analysis Unit and the Preterm Growth Investigator Group
影响因子：
4
作者：
Sun H;Sherrier M;Li H
通讯作者：
Li H
DOI：
10.1073/pnas.0601638103
发表时间：
2006-05-16
影响因子：
11.1
作者：
Bullock, Alex N.;Debreczeni, Judit E.;Knapp, Stefan
通讯作者：
Knapp, Stefan
影响因子：
4.4
作者：
Sankilampi, Ulla;Hannila, Marja-Leena;Dunkel, Leo
通讯作者：
Dunkel, Leo
影响因子：
4.4
作者：
Saari, Antti;Sankilampi, Ulla;Dunkel, Leo
通讯作者：
Dunkel, Leo