Microfibrous Extracellular Matrix Changes the Liver Hepatocyte Energy Metabolism via Integrins

Huang, Tianjiao; Jones, Curtis G.; Chung, Jay H.; Chen, Chengpeng

doi:10.1021/acsbiomaterials.0c01311

Cited by 6 publications

(4 citation statements)

References 92 publications

(184 reference statements)

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“…Of note, ECM also plays an important role in the nutrient uptake, redox status, energy metabolism, and mitochondrial function. The ECM also regulates glucose transport, glycolysis, lipid metabolism, and the TCA cycle [ 120 , 121 , 122 ]. AMPK, the master metabolic regulator, also regulates integrin activity and extracellular matrix assembly [ 123 ].…”

Section: Discussionmentioning

confidence: 99%

Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth

Lien

Zhang

et al. 2021

IJMS

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A well-functioning placenta is crucial for normal gestation and regulates the nutrient, gas, and waste exchanges between the maternal and fetal circulations and is an important endocrine organ producing hormones that regulate both the maternal and fetal physiologies during pregnancy. Placental insufficiency is implicated in spontaneous preterm birth (SPTB). We proposed that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may ultimately result in SPTB. To explore our hypothesis, we performed a RNA-seq study in male and female placentas from women with SPTB (<36 weeks gestation) compared to normal pregnancies (≥38 weeks gestation) to assess the alterations in the gene expression profiles. We focused exclusively on Black women (cases and controls), who are at the highest risk of SPTB. Six hundred and seventy differentially expressed genes were identified in male SPTB placentas. Among them, 313 and 357 transcripts were increased and decreased, respectively. In contrast, only 61 differentially expressed genes were identified in female SPTB placenta. The ingenuity pathway analysis showed alterations in the genes and canonical pathways critical for regulating inflammation, oxidative stress, detoxification, mitochondrial function, energy metabolism, and the extracellular matrix. Many upstream regulators and master regulators important for nutrient-sensing and metabolism were also altered in SPTB placentas, including the PI3K complex, TGFB1/SMADs, SMARCA4, TP63, CDKN2A, BRCA1, and NFAT. The transcriptome was integrated with published human placental metabolome to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the transcriptome were identified in SPTB placentas with fetal sex disparities. Altered energy metabolism, mitochondrial function, inflammation, and detoxification may underly the mechanisms of placental dysfunction in SPTB.

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Section: Discussionmentioning

confidence: 99%

Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth

Lien

Zhang

et al. 2021

IJMS

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“…43 With recent advances in liver tissue engineering, several hepatic differentiation strategies exploring extracellular matrix components have been used to generate hepatocytes or hepatic-like cells in vitro. [43][44][45][46][47][48] In parallel, proteomics-based approaches are increasingly used to answer how decellularization impacts the ECM's composition and its ability to sustain new cells.…”

Section: Liver Extracellular Matrix Before and After Decellularizationmentioning

confidence: 99%

Liver scaffolds obtained by decellularization: A transplant perspective in liver bioengineering

2022

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Liver transplantation is the only definitive treatment for many diseases that affect this organ, however, its quantity and viability are reduced. The study of liver scaffolds based on an extracellular matrix is a tissue bioengineering strategy with great application in regenerative medicine. Collectively, recent studies suggest that liver scaffold transplantation may assist in reestablishing hepatic function in preclinical diseased animals, which represents a great potential for application as a treatment for patients with liver disease in the future. This review focuses on useful strategies to promote liver scaffold transplantation and the main open questions about this context. We outline the current knowledge about ex vivo bioengineered liver transplantation, including the surgical techniques, recipient survival time, scaffold preparation before transplantation, and liver disease models. We also highlight the current limitations and future directions regarding in vivo bioengineering techniques.

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“…To test the second part of the hypothesis (whether integrin overexpression caused the reduction in amino acid levels), we applied a comprehensive blocker (the RGDS peptide [54]) to partially inhibit integrin β1 on cells cultured on flat substrates, and re−analyzed the intracellular amino acids. Based on recent work by us [55], the proper dose of the inhibitor was determined to be 50 µ g/mL. The peptide RGES with the third amino acid replaced by glutamic acid (E) was used as the negative control.…”

Section: Mechanistic Studies Of the Ecm Effectsmentioning

confidence: 99%

Electrospun Microfibers Modulate Intracellular Amino Acids in Liver Cells via Integrin β1

et al. 2021

Self Cite

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Although numerous recent studies have shown the importance of polymeric microfibrous extracellular matrices (ECMs) in maintaining cell behaviors and functions, the mechanistic nexus between ECMs and intracellular activities is largely unknown. Nevertheless, this knowledge will be critical in understanding and treating diseases with ECM remodeling. Therefore, we present our findings that ECM microstructures could regulate intracellular amino acid levels in liver cells mechanistically through integrin β1. Amino acids were studied because they are the fundamental blocks for protein synthesis and metabolism, two vital functions of liver cells. Two ECM conditions, flat and microfibrous, were prepared and studied. In addition to characterizing cell growth, albumin production, urea synthesis, and cytochrome p450 activity, we found that the microfibrous ECM generally upregulated the intracellular amino acid levels. Further explorations showed that cells on the flat substrate expressed more integrin β1 than cells on the microfibers. Moreover, after partially blocking integrin β1 in cells on the flat substrate, the intracellular amino acid levels were restored, strongly supporting integrin β1 as the linking mechanism. This is the first study to report that a non-biological polymer matrix could regulate intracellular amino acid patterns through integrin. The results will help with future therapy development for liver diseases with ECM changes (e.g., fibrosis).

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Microfibrous Extracellular Matrix Changes the Liver Hepatocyte Energy Metabolism via Integrins

Cited by 6 publications

References 92 publications

Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth

Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth

Liver scaffolds obtained by decellularization: A transplant perspective in liver bioengineering

Electrospun Microfibers Modulate Intracellular Amino Acids in Liver Cells via Integrin β1

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