1.Extracellular vesicles: Roles in oocytes and emerging therapeutic opportunities.
Zhongyu ZHAO ; Yinrui SUN ; Renhao GUO ; Junzhi LIANG ; Wanlin DAI ; Yutao JIANG ; Yafan YU ; Yuexin YU ; Lixia HE ; Da LI
Chinese Medical Journal 2025;138(9):1050-1060
The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans
;
Extracellular Vesicles/physiology*
;
Oocytes/cytology*
;
Female
;
Animals
;
Cell Communication/physiology*
2.Crosstalk and the progression of hepatocellular carcinoma.
Lei-Rong GU ; Hui ZHANG ; Juan CHEN ; Sheng-Tao CHENG
Acta Physiologica Sinica 2025;77(2):267-276
Malignant proliferating liver cancer cells possess the ability to detect and respond to various body signals, thereby facilitating tumor growth, invasion, and metastasis. One crucial mechanism through which hepatocellular carcinoma (HCC) cells interpret these signals is crosstalk. Within liver cancer tissues, cancer cells engage in communication with hepatic stellate cells (HSCs), tumor-associated macrophages (TAMs), and immune cells. This interaction plays a pivotal role in regulating the proliferation, invasion, and metastasis of HCC cells. Crosstalk occurs in multiple ways, each characterized by distinct functions. Its molecular mechanisms primarily involve regulating immune cell functions through the expression of specific receptors, such as CD24 and CD47, modulating cell functions by secreting cytokines like transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), and mediating cell growth and proliferation by activating pathways such as Wnt/β-catenin and Hedgehog. A comprehensive understanding of the mechanisms and interactions within crosstalk is essential for unraveling the pathogenesis of HCC. It also opens up new avenues for the development of innovative therapeutic strategies. This article reviews the relationship between crosstalk and the progression of HCC, offering insights and inspiration for future research.
Humans
;
Carcinoma, Hepatocellular/metabolism*
;
Liver Neoplasms/metabolism*
;
Hepatic Stellate Cells/physiology*
;
Disease Progression
;
Signal Transduction/physiology*
;
Transforming Growth Factor beta/metabolism*
;
Cell Proliferation
;
Hedgehog Proteins/metabolism*
;
Tumor-Associated Macrophages
;
Platelet-Derived Growth Factor/metabolism*
;
Cell Communication/physiology*
3.Research progress on the role of extracellular vesicles in the repair of skeletal muscle membrane injury.
Acta Physiologica Sinica 2025;77(5):956-968
The timely and efficient repair of the plasma membrane in skeletal muscle cells following injury is critical for maintaining cellular function and tissue integrity. Extracellular vesicles (EVs) play a pivotal role in this process through multi-level mechanisms. This review systematically summarizes the generation, secretion, and multifunctional roles of EVs in the repair of skeletal muscle plasma membrane damage: (1) removing damaged membrane fragments and cellular debris via endocytosis and exocytosis to maintain plasma membrane stability; (2) fusing with the injured plasma membrane to supply essential components for membrane repair and restore membrane integrity; and (3) serving as a vital mediator of intercellular communication, transmitting repair signals, promoting intercellular interactions, and orchestrating multi-level responses to facilitate tissue regeneration and functional recovery. Additionally, this article explores the potential applications of EVs in the treatment of exercise-induced injuries and muscular diseases, aiming to provide theoretical insights and novel strategies for future research and EV-based therapeutic approaches.
Extracellular Vesicles/physiology*
;
Humans
;
Muscle, Skeletal/physiology*
;
Cell Membrane/physiology*
;
Animals
;
Regeneration/physiology*
;
Exocytosis/physiology*
;
Endocytosis/physiology*
;
Cell Communication/physiology*
4.Pathophysiological implications of cellular senescence and prospects for novel anti-aging drugs.
Acta Physiologica Sinica 2023;75(6):847-863
Chronological aging is the leading risk factor for human diseases, while aging at the cellular level, namely cellular senescence, is the fundamental driving force of organismal aging. The impact of cellular senescence on various life processes, including normal physiology, organismal aging and the progress of various age-related pathologies, has been largely ignored for a long time. However, with recent advancement in relevant fields, cellular senescence has become the core of aging biology and geriatric medicine. Although senescent cells play important roles in physiological processes including tissue repair, wound healing, and embryonic development, they can also contribute to tissue dysfunction, organ degeneration and various pathological conditions during adulthood. Senescent cells exert paracrine effects on neighboring cells in tissue microenvironments by developing a senescence-associated secretory phenotype, thus maintaining long-term and active intercellular communications that ultimately results in multiple pathophysiological effects. This is regarded as one of the most important discoveries in life science of this century. Notably, selective elimination of senescent cells through inducing their apoptosis or specifically inhibiting the senescence-associated secretory phenotype has shown remarkable potential in preclinical and clinical interventions of aging and age-related diseases. This reinforces the belief that senescent cells are the key drug target to alleviate various aging syndromes. However, senescent cells exhibit heterogeneity in terms of form, function and tissue distribution, and even differ among species, which presents a challenge for the translation of significant research achievements to clinical practice in future. This article reviews and discusses the characteristics of senescent cells, current targeting strategies and future trends, providing useful and valuable references for the rapidly blooming aging biology and geriatric medicine.
Humans
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Adult
;
Aged
;
Cellular Senescence/genetics*
;
Aging
;
Apoptosis
;
Cell Communication
;
Wound Healing/physiology*
5.Advances in the Regulation of Follicular Development by Extracellular Vesicles and Non-Coding RNAs.
Acta Academiae Medicinae Sinicae 2023;45(5):821-826
Extracellular vesicles (EV),nanoscale vesicles encapsulated by phospholipid bilayers,are rich in biological molecules such as nucleic acids,metabolites,proteins,and lipids derived from parental cells.They are mainly involved in intercellular communication,signal transmission,and material transport and affect the functions of target cells.Ovulation disorders account for a higher proportion in the factors causing infertility which demonstrates increasing incidence year by year.Non-coding RNAs participate in a series of physiological and pathological processes of follicular development,playing a key role in female infertility.This review systematically introduces the types and biological roles of EV and elaborates on the regulation of follicular development from the effects of EV and non-coding RNAs on granulosa cell function,oocyte maturation,ovulation,luteal formation,and steroid hormone synthesis,providing a new idea and a breakthrough point for the diagnosis and treatment of infertility.
Female
;
Humans
;
Oogenesis/physiology*
;
Granulosa Cells
;
Extracellular Vesicles/physiology*
;
Cell Communication
;
RNA, Untranslated
;
Infertility
6.Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling.
Min WEI ; Yanping SUN ; Shouzhen LI ; Yunuo CHEN ; Longfei LI ; Minghao FANG ; Ronghua SHI ; Dali TONG ; Jutao CHEN ; Yuqian MA ; Kun QU ; Mei ZHANG ; Tian XUE
Protein & Cell 2023;14(8):603-617
Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
Animals
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Mice
;
Dark Adaptation
;
Light
;
Retina
;
Retinal Cone Photoreceptor Cells/metabolism*
;
Adaptation, Ocular
;
Neuroglia/physiology*
;
Cell Communication
;
Thyroid Hormones
7.Exosome-mediated regulatory mechanisms in skeletal muscle: a narrative review.
Zhaolu WANG ; Jinjin YANG ; Xiaohui SUN ; Xi SUN ; Gongshe YANG ; Xin'e SHI
Journal of Zhejiang University. Science. B 2023;24(1):1-14
Skeletal muscle plays a paramount role in physical activity, metabolism, and energy balance, while its homeostasis is being challenged by multiple unfavorable factors such as injury, aging, or obesity. Exosomes, a subset of extracellular vesicles, are now recognized as essential mediators of intercellular communication, holding great clinical potential in the treatment of skeletal muscle diseases. Herein, we outline the recent research progress in exosomal isolation, characterization, and mechanism of action, and emphatically discuss current advances in exosomes derived from multiple organs and tissues, and engineered exosomes regarding the regulation of physiological and pathological development of skeletal muscle. These remarkable advances expand our understanding of myogenesis and muscle diseases. Meanwhile, the engineered exosome, as an endogenous nanocarrier combined with advanced design methodologies of biomolecules, will help to open up innovative therapeutic perspectives for the treatment of muscle diseases.
Exosomes/physiology*
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Muscle, Skeletal/metabolism*
;
Cell Communication
;
Homeostasis
8.Research progress of tunneling nanotube in bone biology.
Jin Biao QIANG ; Xiao Ling WANG ; Xue Ying BAI ; Xin Yi FAN ; Ce SHI
Chinese Journal of Stomatology 2023;58(1):86-91
Tunneling nanotube (TNT) is a newly discovered communication mode between animal cells in recent years, which have important physiological and pathological significance. However, the role of TNT in bone biology is still unclear. At present, there are many reports about tunneling nanotubes in bone marrow mesenchymal stem cells, osteoclast precursor cells, osteoblasts and immune cells. This review describes the research advances of TNT and its research progress in bone biology. It looks forward to the research direction of TNT in oral and maxillofacial bone development and bone biology, to provide new strategies for the maintenance of bone homeostasis and the treatment of bone diseases.
Animals
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Bone and Bones
;
Nanotubes
;
Osteoclasts
;
Biology
;
Cell Communication/physiology*
9.Cooperation-based sperm clusters mediate sperm oviduct entry and fertilization.
Yongcun QU ; Qi CHEN ; Shanshan GUO ; Chiyuan MA ; Yonggang LU ; Junchao SHI ; Shichao LIU ; Tong ZHOU ; Taichi NODA ; Jingjing QIAN ; Liwen ZHANG ; Xili ZHU ; Xiaohua LEI ; Yujing CAO ; Wei LI ; Wei LI ; Nicolas PLACHTA ; Martin M MATZUK ; Masahito IKAWA ; Enkui DUAN ; Ying ZHANG ; Hongmei WANG
Protein & Cell 2021;12(10):810-817
Animals
;
Antigens, Surface/genetics*
;
Cell Communication/genetics*
;
Copulation/physiology*
;
Fallopian Tubes/metabolism*
;
Female
;
Fertilization/genetics*
;
GPI-Linked Proteins/genetics*
;
Gene Expression Regulation
;
Genes, Reporter
;
Green Fluorescent Proteins/metabolism*
;
Litter Size
;
Luminescent Proteins/metabolism*
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Mitochondria/metabolism*
;
Reproduction/genetics*
;
Signal Transduction
;
Sperm Count
;
Sperm Motility/genetics*
;
Spermatozoa/metabolism*
;
Uterus/metabolism*
10.MicroRNAs in tumor immunity: functional regulation in tumor-associated macrophages.
Chong CHEN ; Jia-Ming LIU ; Yun-Ping LUO
Journal of Zhejiang University. Science. B 2020;21(1):12-28
Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and are critical for cancer initiation and progression. MicroRNAs (miRNAs) could notably influence the phenotype of TAMs through various targets and signal pathways during cancer progression due to their post-transcriptional regulation. In this review, we discuss mainly the regulatory function of miRNAs on macrophage differentiation, functional polarization, and cellular crosstalk. Firstly, during the generation process, miRNAs take part in the differentiation from myeloid cells to mature macrophages, and this maturation process directly influences their recruitment into the TME, attracted by tumor cells. Secondly, macrophages in the TME can be either tumor-promoting or tumor-suppressing, depending on their functional polarization. Large numbers of miRNAs can influence the polarization of macrophages, which is crucial for tumor progression, including tumor cell invasion, intravasation, extravasation, and premetastatic site formation. Thirdly, crosstalk between tumor cells and macrophages is essential for TME formation and tumor progression, and miRNAs can be the mediator of communication in different forms, especially when encapsulated in microvesicles or exosomes. We also assess the potential value of certain macrophage-related miRNAs (MRMs) as diagnostic and prognostic markers, and discuss the possible development of MRM-based therapies.
Cell Communication
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Cell Differentiation
;
Cell Polarity
;
Humans
;
Macrophages/physiology*
;
MicroRNAs/physiology*
;
Myeloid Cells/cytology*
;
Neoplasms/therapy*
;
Tumor Microenvironment

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