人肺发育过程中 CD44 和 RHAMM 的表达模式。

CD44 and RHAMM expression patterns in the human developing lung.

机构信息

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.

出版信息

Pediatr Res. 2021 Jan;89(1):134-142. doi: 10.1038/s41390-020-0873-y. Epub 2020 Apr 20.

DOI:10.1038/s41390-020-0873-y

PMID:32311697

Abstract

BACKGROUND

The hyaluronan (HA) receptors CD44 and RHAMM (CD168) are involved in cellular proliferation, differentiation, and motility. As previously investigated, HA and RHAMM expression in human neonatal lungs correlates to gestational age (GA) and air content.

METHODS

CD44 immunofluorescence was analyzed in postmortem lung samples from infants (n = 93; 22-41 GA) by digital image analysis together with clinical data, including RHAMM expression, lung air, and HA content by hierarchical clustering.

RESULTS

Five groups were defined according to RHAMM/CD44 expression, GA, and postnatal age (PNA): extremely to very preterm (EVP; 22-31 GA; Groups 1-2), moderately preterm to term (MPT; 31-41 GA; Groups 3-4), and mixed preterm to term (27-40 GA; Group 5). CD44 correlated linearly with RHAMM in MPT (r = 0.600; p < 0.004). In EVP, high CD44 and low RHAMM corresponded with high PNA and lung air content independently of HA and GA (Group 1 vs 2; p < 0.05). In MPT, high and low CD44 corresponded with low and high RHAMM independently of GA, HA, and lung air content (Group 3 vs 4; p < 0.001). No correlation between CD44 and GA/PNA at death was observed.

CONCLUSIONS

A linear correlation between CD44 and RHAMM expression occurs during the late saccular phase of lung development at birth, whereas postnatal influences on CD44 and RHAMM expression in extremely to very preterm infants cannot be excluded.

IMPACT

The interplay between CD44 and RHAMM, two receptors of hyaluronic acid, can be dependent on the lung developmental stage at birth. This is the second study that analyzes the distribution pattern of CD44 in the human lung during development and the first study performed with quantitative analysis of CD44 expression together with RHAMM expression in the human lung. Our results suggest a relationship in a subset of infants between CD44 and RHAMM expression, which appears at birth during the late saccular stage but not during the earlier stages of lung development.

摘要

背景

透明质酸（HA）受体 CD44 和 RHAMM（CD168）参与细胞增殖、分化和迁移。此前的研究表明，人新生儿肺中的 HA 和 RHAMM 表达与胎龄（GA）和空气含量相关。

方法

通过数字图像分析，对 93 例（22-41GA）尸检肺组织中的 CD44 免疫荧光进行分析，并结合临床数据，包括 RHAMM 表达、肺空气和 HA 含量进行层次聚类分析。

结果

根据 RHAMM/CD44 表达、GA 和生后年龄（PNA）将 93 例婴儿分为五组：极早产儿至非常早产儿（EVP；22-31GA；第 1-2 组）、中度早产儿至足月产儿（MPT；31-41GA；第 3-4 组）和混合早产儿至足月产儿（27-40GA；第 5 组）。MPT 中 CD44 与 RHAMM 呈线性相关（r=0.600；p<0.004）。EVP 中，高 CD44 和低 RHAMM 与高 PNA 和肺空气含量独立相关，而与 HA 和 GA 无关（第 1 组与第 2 组；p<0.05）。在 MPT 中，高 CD44 和低 RHAMM 与低 GA、HA 和肺空气含量独立相关（第 3 组与第 4 组；p<0.001）。在死亡时，未观察到 CD44 与 GA/PNA 之间存在相关性。

结论

在出生时的肺泡晚期发育阶段，CD44 和 RHAMM 表达之间存在线性相关性，而极早产儿和非常早产儿的 CD44 和 RHAMM 表达的出生后影响尚不能排除。

意义

透明质酸的两种受体 CD44 和 RHAMM 之间的相互作用可能取决于出生时的肺发育阶段。这是第二项分析人类肺中 CD44 分布模式的研究，也是第一项对人类肺中 CD44 表达与 RHAMM 表达进行定量分析的研究。我们的研究结果表明，在一组婴儿中，CD44 和 RHAMM 表达之间存在一种关系，这种关系出现在出生时的肺泡晚期阶段，但不在肺发育的早期阶段。