The vasculature, present in all tissues, has long been regarded as a mere conduit for oxygen, nutrients, and waste. However, recent research has unveiled endothelial cells as dynamic regulators of tissue homeostasis, capable of influencing organ growth and regeneration through secreted factors called angiocrines [1-4]. The discovery of angiocrines as key mediators of endothelial-parenchymal interactions is transforming our understanding of regenerative medicine and targeted therapies. Follert et al. hypothesize that flow-responsive angiocrines act as central orchestrators of tissue regrowth and regeneration, triggered by mechanical stimuli on endothelial cells following partial organ resection [5]. The currently known liver, lung, and kidney angiocrines are presented with special focus on the recently identified myeloid-derived growth factor (MYDGF) and hepatocyte growth factor (HGF). Different tissues have very different abilities to regenerate after injury or surgical resection. In both mice and humans, the liver exhibits remarkable regenerative capacity, capable of restoring its mass within weeks after losing more than half of its volume, whereas, for example the heart has a very poor regeneration capacity. Compared to the liver, the kidney and lung show limited and delayed compensatory growth, highlighting a spectrum of regenerative potential across organs. Elegant previous experiments have demonstrated that liver regrowth is dependent on angiogenic response and the production of angiocrines, highlighting the crucial role of endothelial cells in the liver growth and regeneration process [6, 7]. To date, several different proteins have been identified as angiocrines produced by the liver endothelial cells with growth-promoting effects. Less is known about angiocrines regulating growth and regeneration in the kidney and lung. Thus, understanding the organ-specific angiocrine signaling during tissue growth, homeostasis, and disease is a key for the development of new therapeutic approaches to maintain organ health and initiate organ renewal. Endothelial cells experience laminar shear stress induced by blood flow, which is presicely adjusted to the physiological needs of each organ. Investigating how flow-responsive angiocrines vary between physiological stresses, such as exercise, and pathological conditions (organ resection or trauma), could unveil distinct regenerative mechanisms. Blood flow, blood pressure, and the amount of mechanical stretching to endothelial cells can rapidly change, for example, in response to acute trauma or heavy exercise. Severe changes in blood flow also occur after partial organ resection, which is the main topic of this hypothesis [5]. The hypothesis also touches upon the pivotal role of angiocrines in tumor progression, suggesting that angiocrines regulate cancer cell behavior and metastasis. Vascular morphology and function are very different in solid tumors compared to healthy tissues, affecting blood flow patterns and mechanoelastic stretch in endothelial cells. Several angiocrines have been shown to influence tumor cell dynamics, but future research should focus on identifying tumor type-specific angiocrines to inform targeted therapies. Understanding tumor-specific angiocrines and their interplay with the tumor microenvironment could pave the way for targeted therapies to inhibit tumor progression Our understanding of endothelial cells and their angiocrine secretome in regulating organ-specific development, maintenance, and regeneration is fast expanding, with vast potential for therapeutic exploration. It is important to note that, in addition to proteins, metabolites or small molecules are also produced and released by endothelial cells. These different types of angiocrines can function locally on adjacent cells or travel through the bloodstream to distant organs, underscoring the complexity and versatility of angiocrine signaling. Future studies will leverage novel single-cell techniques to decode angiocrine diversity across organotypic niches and health states, offering precision interventions for different diseases. This article comments on the hypothesis paper by Paula Follert, Linda Große-Segerath, and Eckhard Lammert, https://doi.org/10.1002/bies.202400207

Riikka Kivelä

BioEssays

分子 - 细胞 - 生物医学 - 生理学 - 转化研究 - 系统 - 鼓励假设 BIOESSAYS 是一份经过同行评审、审查和讨论的期刊。我们的目标是在分子、遗传、细胞或生理维度上发表当代生物学的新颖见解、前瞻性评论和评论，并作为这些领域新思想的讨论论坛。另一个目标是鼓励在有机体研究、系统方法和生态系统方面的跨学科和综合生物学，在适当的情况下。

BioEssays is a peer-reviewed journal that focuses on molecular, cellular, biomedical, physiological, translational research, and systems biology. Our aim is to publish novel insights, forward-looking reviews, and comprehensive commentaries in contemporary biology, serving as a forum for discussion of new ideas in these fields. Additionally, we encourage interdisciplinary and integrative biology research in organism studies, systems approaches, and ecosystems where appropriate.

BioEssays 是一本经过同行评审的期刊，专注于分子、细胞、生物医学、生理学、转化研究和系统生物学等领域。我们的目标是发表当代生物学的新颖见解、前瞻性评论和综合评述，并为这些领域的新思想提供讨论平台。此外，我们还鼓励在有机体研究、系统方法和生态系统方面的跨学科和综合生物学研究。

Category	Quartile
生物学	3
生物学, 生物学	3
生物学, 生化与分子生物学	4

Decoding Angiocrine Signaling: Endothelial Cells as Drivers of Organ Regeneration and Homeostasis

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