Dataset Information

Baicalin Promotes Mammary Gland Development via Steroid-Like Activities.

ABSTRACT: Baicalin, the main flavonoid component extracted from Scutellaria roots, has a variety of biological activities and is therefore used in the treatment of many kinds of diseases. However, whether baicalin affects the normal development of tissues and organs is still unclear. Here, using a mouse mammary gland model, we investigated the effects of baicalin on the expansion of mammary stem cells (MaSCs) and mammary development, as well as breast cancer progression. Interestingly, we found that baicalin administration significantly accelerates duct elongation at puberty, and promotes alveolar development and facilitates milk secretion during pregnancy. Furthermore, self-renewal of MaSCs was significantly promoted in the presence of baicalin. Moreover, in a tumor xenograft model, baicalin promoted tumor growth of the MDA-MB-231 cell line, but suppressed tumor growth of the ZR-751 cell line. Mechanistically, baicalin can induce expression of the protein C receptor, while inhibiting the expression of the estrogen receptor. Transcriptome analysis revealed that baicalin is involved in signaling pathways related to mammary gland development, immune response, and cell cycle control. Taken together, our results from comprehensive investigation of the biological activity of baicalin provide a theoretical basis for its rational clinical application.

SUBMITTER: Chen W

PROVIDER: S-EPMC8290356 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Baicalin Promotes Mammary Gland Development via Steroid-Like Activities.

Chen Weizhen W Wei Wei W Yu Liya L Zhang Xin X Huang Fujing F Zheng Qiping Q Wang Lingli L Cai Cheguo C

Frontiers in cell and developmental biology 20210706

Baicalin, the main flavonoid component extracted from <i>Scutellaria</i> roots, has a variety of biological activities and is therefore used in the treatment of many kinds of diseases. However, whether baicalin affects the normal development of tissues and organs is still unclear. Here, using a mouse mammary gland model, we investigated the effects of baicalin on the expansion of mammary stem cells (MaSCs) and mammary development, as well as breast cancer progression. Interestingly, we found tha ...[more]

PMID: 34295892

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Project description:P190A and p190B Rho GTPase activating proteins (GAPs) are essential genes that have distinct, but overlapping roles in the developing nervous system. Previous studies from our laboratory demonstrated that p190B is required for mammary gland morphogenesis, and we hypothesized that p190A might have a distinct role in the developing mammary gland. To test this hypothesis, we examined mammary gland development in p190A-deficient mice. P190A expression was detected by in situ hybridization in the developing E14.5day embryonic mammary bud and within the ducts, terminal end buds (TEBs), and surrounding stroma of the developing virgin mammary gland. In contrast to previous results with p190B, examination of p190A heterozygous mammary glands demonstrated that p190A deficiency disrupted TEB morphology, but did not significantly delay ductal outgrowth indicating haploinsufficiency for TEB development. To examine the effects of homozygous deletion of p190A, embryonic mammary buds were rescued by transplantation into the cleared fat pads of SCID/Beige mice. Complete loss of p190A function inhibited ductal outgrowth in comparison to wildtype transplants (51% vs. 94% fat pad filled). In addition, the transplantation take rate of p190A deficient whole gland transplants from E18.5 embryos was significantly reduced compared to wildtype transplants (31% vs. 90%, respectively). These results suggest that p190A function in both the epithelium and stroma is required for mammary gland development. Immunostaining for p63 demonstrated that the myoepithelial cell layer is disrupted in the p190A deficient glands, which may result from the defective cell adhesion between the cap and body cell layers detected in the TEBs. The number of estrogen- and progesterone receptor-positive cells, as well as the expression levels of these receptors was increased in p190A deficient outgrowths. These data suggest that p190A is required in both the epithelial and stromal compartments for ductal outgrowth and that it may play a role in mammary epithelial cell differentiation.

Project description:The mammary gland is a unique organ as most of its development occurs after birth through stages of proliferation, differentiation and apoptosis that are tightly regulated by circulating hormones and growth factors. Throughout development, hormonal cues induce the regulation of different pathways, ultimately leading to differential transcription and expression of genes involved in this process, but also in the activation or inhibition of post-transcriptional mechanisms of regulation. However, the role of microRNAs (miRNAs) in the different phases of mammary gland remodeling is still poorly understood. The objectives of this study were to analyze the expression of miRNA in key stages of mammary gland development in mice and to determine whether it could be associated with hormonal variation between stages. To do so, miRNAs were isolated from mouse mammary glands at stages of adulthood, pregnancy, lactation and involution, and sequenced. Results showed that 490, 473, 419, and 460 miRNAs are detected in adult, pregnant, lactating and involuting mice, respectively, most of them being common to all four groups, and 58 unique to one stage. Most genes could be divided into six clusters of expression, including two encompassing the highest number of miRNA (clusters 1 and 3) and showing opposite profiles of expression, reaching a peak at adulthood and valley at lactation, or showing the lowest expression at adulthood and peaking at lactation. GO and KEGG analyses suggest that the miRNAs differentially expressed between stages influence the expression of targets associated with mammary gland homeostasis and hormone regulation. To further understand the links between miRNA expression and hormones involved in mammary gland development, miRNAs were then sequenced in breast cells exposed to estradiol, progesterone, prolactin and oxytocin. Four, 38, 24 and 66 miRNAs were associated with progesterone, estradiol, prolactin, and oxytocin exposure, respectively. Finally, when looking at miRNAs modulated by the hormones, differentially expressed during mammary gland development, and having a pattern of expression that could be correlated with the relative levels of hormones known to be found in vivo, 16 miRNAs were identified as likely regulated by circulating hormones. Overall, our study brings a better understanding of the regulation of miRNAs throughout mammary gland development and suggests that there is a relationship between their expression and the main hormones involved in mammary gland development. Future studies will examine this role more in detail.

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Baicalin Promotes Mammary Gland Development via Steroid-Like Activities.

Publications

Baicalin Promotes Mammary Gland Development via Steroid-Like Activities.

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