Hyaluronan Induces a Mitochondrial Functional Switch in Fast-Proliferating Human Mesenchymal Stem

Solís, Mairim Alexandra; Wei, Yau‐Huei; Chang, Cheng-Yen; Chen, Yu; Huang, Lynn L.H.

doi:10.15283/ijsc19004

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…S2D ). Similar results have also emerged in the other reports [ 27 ]. We noticed that in addition to glycolysis and OXPHOS, mitochondrial substrate-level phosphorylation (mSLP) can also generate sufficient ATP to meet cellular demands in the presence or absence of oxygen [ 22 , 23 ].…”

Section: Resultssupporting

confidence: 92%

Mitochondrial homeostasis regulates definitive endoderm differentiation of human pluripotent stem cells

Yan

et al. 2022

Cell Death Discov.

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Cellular organelles play fundamental roles in almost all cell behaviors. Mitochondria have been reported to be functionally linked to various biological processes, including reprogramming and pluripotency maintenance. However, very little about the role of mitochondria has been revealed in human early development and lineage specification. Here, we reported the characteristics and function of mitochondria during human definitive endoderm differentiation. Using a well-established differentiation system, we first investigated the change of mitochondrial morphology by comparing undifferentiated pluripotent stem cells, the intermediate mesendoderm cells, and differentiated endoderm cells, and found that mitochondria were gradually elongated and matured along differentiation. We further analyzed the expression pattern of mitochondria-related genes by RNA-seq, indicating that mitochondria became active during differentiation. Supporting this notion, the production of adenosine triphosphate (ATP) and reactive oxygen species (ROS) was increased as well. Functionally, we utilized chemicals and genome editing techniques, which could interfere with mitochondrial homeostasis, to determine the role of mitochondria in human endoderm differentiation. Treatment with mitochondrial inhibitors, or genetic depletion of mitochondrial transcription factor A (TFAM), significantly reduced the differentiation efficiency of definitive endoderm. In addition, the defect in endoderm differentiation due to dysfunctional mitochondria could be restored to some extent by the addition of ATP. Moreover, the clearance of excessive ROS due to dysfunctional mitochondria by N-acetylcysteine (NAC) improved the differentiation as well. We further found that ATP and NAC could partially replace the growth factor activin A for definitive endoderm differentiation. Our study illustrates the essential role of mitochondria during human endoderm differentiation through providing ATP and regulating ROS levels, which may provide new insight for metabolic regulation of cell fate determination.

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Section: Resultssupporting

confidence: 92%

Mitochondrial homeostasis regulates definitive endoderm differentiation of human pluripotent stem cells

Yan

et al. 2022

Cell Death Discov.

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“…4 ). In human placenta-derived mesenchymal stem cells, HA at around 1 μg/mL acts as an inducer that switches on mitochondria function to enhance the glycolysis progression with about twice the amount of ATP and lactate production [ 134 ]. Radioactive element 14 C was used to label HA, oral or intravenous administration in male SD rats.…”

Section: Pre-metastatic Barometer In the Tumor Microenvironmentmentioning

confidence: 99%

‘Two-faces’ of hyaluronan, a dynamic barometer of disease progression in tumor microenvironment

Liu

Wang

et al. 2023

Discov Onc

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Hyaluronan (HA) is a linear polysaccharide consisting of disaccharide units which are the d-glucuronic acid and n-acetyl-d-glucosamine. As the largest component of the extracellular matrix in microenvironment, HA polymers with different molecular weights vary in properties to molecular biology function. High molecular weight HA (HMW-HA) is mainly found in normal tissue or physiological condition, and exhibits lubrication and protection properties due to its good water retention and viscoelasticity. On the other hand, an increase in HA catabolism leads to the accumulation of low molecular weight HA (LMW-HA) under pathological circumstances such as inflammation, pre-cancerous and tumor microenvironment. LMW-HA acts as extracellular signals to enhance tumorigenic and metastatic phenotype, such as energy reprogramming, angiogenesis and extracellular matrix (ECM) remodeling. This review discusses the basic properties of this simplest carbohydrate molecule in ECM with enormous potential, and its regulatory role between tumorigenesis and microenvironmental homeostasis. The extensive discoveries of the mechanisms underlying the roles of HA in various physiological and pathological processes would provide more information for future research in the fields of biomimetic materials, pharmaceutical and clinical applications.

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“…Indeed, HARE’s uptake of HMW HA in WI-38 fibroblasts attenuated DNA damage induced by both exogenous and endogenous oxidants [ 84 ]. Likewise, HA is postulated to attenuate ROS effects in mesenchymal stem cells [ 85 ].…”

Section: Ha-associated Ros Effects In Tissue Homeostasismentioning

confidence: 99%

Hyaluronan and Reactive Oxygen Species Signaling—Novel Cues from the Matrix?

et al. 2023

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Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) localized to the cell surface and the tissue extracellular matrix (ECM). It is composed of disaccharides containing glucuronic acid and N-acetylglucosamine, is synthesized by the HA synthase (HAS) enzymes and is degraded by hyaluronidase (HYAL) or reactive oxygen and nitrogen species (ROS/RNS) actions. HA is deposited as a high molecular weight (HMW) polymer and degraded to low molecular weight (LMW) fragments and oligosaccharides. HA affects biological functions by interacting with HA-binding proteins (hyaladherins). HMW HA is anti-inflammatory, immunosuppressive, and antiangiogenic, whereas LMW HA has pro-inflammatory, pro-angiogenetic, and oncogenic effects. ROS/RNS naturally degrade HMW HA, albeit at enhanced levels during tissue injury and inflammatory processes. Thus, the degradation of endothelial glycocalyx HA by increased ROS challenges vascular integrity and can initiate several disease progressions. Conversely, HA exerts a vital role in wound healing through ROS-mediated HA modifications, which affect the innate immune system. The normal turnover of HA protects against matrix rigidification. Insufficient turnover leads to increased tissue rigidity, leading to tissue dysfunction. Both endogenous and exogenous HMW HA have a scavenging capacity against ROS. The interactions of ROS/RNS with HA are more complex than presently perceived and present an important research topic.

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Hyaluronan Induces a Mitochondrial Functional Switch in Fast-Proliferating Human Mesenchymal Stem

Cited by 6 publications

References 38 publications

Mitochondrial homeostasis regulates definitive endoderm differentiation of human pluripotent stem cells

Mitochondrial homeostasis regulates definitive endoderm differentiation of human pluripotent stem cells

‘Two-faces’ of hyaluronan, a dynamic barometer of disease progression in tumor microenvironment

Hyaluronan and Reactive Oxygen Species Signaling—Novel Cues from the Matrix?

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