scholarly journals Exosome-Mimetic Nanovesicles from Hepatocytes promote hepatocyte proliferation in vitro and liver regeneration in vivo

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Jun-Yi Wu ◽  
An-Lai Ji ◽  
Zhong-xia Wang ◽  
Guang-Hui Qiang ◽  
Zhen Qu ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Hepatocyte Proliferation ◽  
Proliferation In Vitro

scholarly journals Exosomal circ-RBM23 sponging miR-139-5p to promote liver regeneration through RRM2/AKT/mTOR pathway

2021 ◽  
Author(s):  
Guolin He ◽  
Yu Fu ◽  
Zeyi Guo ◽  
Honglei Zhu ◽  
Lei Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Membrane Vesicles ◽  
Hepatocyte Proliferation ◽  
Intercellular Interaction ◽  
Proliferative Effect ◽  
Proliferation In Vitro

Abstract BackgroundExosomes are small nano-size membrane vesicles and are involved in intercellular interaction. Here, we examined if exosomes obtained from human placental stem cells promote liver regeneration after partial hepatectomy. MethodsExosomes generated from primary human placental stem cells were isolated and characterized. Cell co-culture model was used to clarify whether exosomes can induce hepatocytes proliferation in vitro . Partial hepatectomy mouse model was used to evaluate whether exosomes can promote hepatocytes proliferation in vivo . ResultsIt is found that human placental-derived stem cells exosomes (hPDSCs-exo) can induce hepatocyte proliferation in vitro and in vivo . Mechanistically, exosomal circ-RBM23 served as a ceRNA for miR-139-5p, regulated RRM2 and accelerated proliferation through AKT/mTOR pathways. Ablation of exosomal circ-RBM23 suppressed the proliferative effect of exosomes. ConclusionsThe hPMSCs exosomal circ-RBM23 stimulated cell proliferation and liver regeneration after 70% partial hepatectomy by regulated RRM2. Our findings highlight a potential novel therapeutic avenue for liver regeneration after hepatectomy.

PXR stimulates growth factor-mediated hepatocyte proliferation by cross-talk with the FOXO transcription factor

2016 ◽  
Vol 473 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Ryota Shizu ◽  
Taiki Abe ◽  
Satoshi Benoki ◽  
Miki Takahashi ◽  
Susumu Kodama ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Growth Factor ◽  
Liver Injury ◽  
Hepatocyte Proliferation ◽  
Suppressor Genes ◽  
Proliferation In Vitro ◽  
Murine Hepatocyte

Activation of PXR enhanced growth factor- and liver injury-mediated murine hepatocyte proliferation in vitro and in vivo. Mechanistic analyses suggest that activated PXR down-regulates the expression of cell-cycle suppressor genes by inhibiting their FOXO3-dependent transcription.

scholarly journals Genes Inducing iPS Phenotype Play a Role in Hepatocyte Survival and Proliferation In Vitro and Liver Regeneration In Vivo

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Vishakha Bhave ◽  
Shirish Paranjpe ◽  
William C Bowen ◽  
Shashikiran Donthamsetty ◽  
Aaron Bell ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Proliferation In Vitro

scholarly journals Genes inducing iPS phenotype play a role in hepatocyte survival and proliferation in vitro and liver regeneration in vivo

Hepatology ◽  
2011 ◽  
Vol 54 (4) ◽  
pp. 1360-1370 ◽  
Author(s):  
Vishakha S. Bhave ◽  
Shirish Paranjpe ◽  
William C. Bowen ◽  
Shashikiran Donthamsetty ◽  
Aaron W. Bell ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Proliferation In Vitro

scholarly journals Partial Hepatectomy-Induced Upregulation of miR-1907 Accelerates Liver Regeneration by Activation Autophagy

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Tianfei Lu ◽  
Jun Hao ◽  
Chuan Shen ◽  
Guangxiang Gu ◽  
Jianjun Zhang ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Weight Ratio ◽  
Underlying Mechanism ◽  
Hepatocyte Proliferation ◽  
Pharmacological Intervention ◽  
Body Weight Ratio

Liver regeneration after partial hepatectomy (PH) is a highly orchestrated biological process in which synchronized hepatocyte proliferation is induced after massive liver mass loss. Hepatocyte proliferation could be regulated by multiple signals, such as miRNAs and autophagy, but underlying mechanism remains unclear. Here a functional miRNA during liver regeneration was identified and its underlying mechanism was delineated in vitro and in vivo. We found that miR-1907 was highly upregulated during liver regeneration after 2/3 PH at various timepoints. The level of miR-1907 was also increased in normal liver cell line treated with HGF at different concentrations. Functionally, miR-1907 enhanced hepatocyte proliferation in vitro and in vivo, and the liver/body weight ratio in miR-1907-overexpressed mice was significantly higher in comparison to the control mice after 2/3 PH. Forced expression of miR-1907 promoted autophagy activation of hepatocyte. Importantly, autophagy inhibition significantly attenuated miR-1907-induced hepatocyte proliferation and the liver/body weight ratio. Finally, GSK3β, a suppressor of autophagy signaling, was identified as the direct target gene of miR-1907. Taken together, miR-1907 accelerates hepatocyte proliferation during liver regeneration by activating autophagy; thus pharmacological intervention regulating miR-1907/autophagy axis may be therapeutically beneficial in liver transplantation and liver failure by inducing liver regeneration.

scholarly journals Ethanolamine modulates the rate of rat hepatocyte proliferation in vitro and in vivo

1997 ◽  
Vol 94 (14) ◽  
pp. 7320-7325 ◽  
Author(s):  
H. Sasaki ◽  
H. Kume ◽  
A. Nemoto ◽  
S. Narisawa ◽  
N. Takahashi
Keyword(s):  
Hepatocyte Proliferation ◽  
Rat Hepatocyte ◽  
Proliferation In Vitro

scholarly journals Endothelial transcription factor KLF2 negatively regulates liver regeneration via induction of activin A

2017 ◽  
Vol 114 (15) ◽  
pp. 3993-3998 ◽  
Author(s):  
Yosif Manavski ◽  
Tobias Abel ◽  
Junhao Hu ◽  
Dina Kleinlützum ◽  
Christian J. Buchholz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Liver Regeneration ◽  
Serum Levels ◽  
Capillary Density ◽  
Activin A ◽  
Hepatocyte Proliferation ◽  
Deficient Mice

Endothelial cells (ECs) not only are important for oxygen delivery but also act as a paracrine source for signals that determine the balance between tissue regeneration and fibrosis. Here we show that genetic inactivation of flow-induced transcription factor Krüppel-like factor 2 (KLF2) in ECs results in reduced liver damage and augmentation of hepatocyte proliferation after chronic liver injury by treatment with carbon tetrachloride (CCl4). Serum levels of GLDH3 and ALT were significantly reduced in CCl4-treated EC-specific KLF2-deficient mice. In contrast, transgenic overexpression of KLF2 in liver sinusoidal ECs reduced hepatocyte proliferation. KLF2 induced activin A expression and secretion from endothelial cells in vitro and in vivo, which inhibited hepatocyte proliferation. However, loss or gain of KLF2 expression did not change capillary density and liver fibrosis, but significantly affected hepatocyte proliferation. Taken together, the data demonstrate that KLF2 induces an antiproliferative secretome, including activin A, which attenuates liver regeneration.

scholarly journals Dicer-dependent production of microRNA221 in hepatocytes inhibits p27 and is required for liver regeneration in mice

2017 ◽  
Vol 312 (5) ◽  
pp. G464-G473 ◽  
Author(s):  
Yuki Oya ◽  
Ryota Masuzaki ◽  
Daisuke Tsugawa ◽  
Kevin C. Ray ◽  
Yongchao Dou ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Hepatocyte Proliferation ◽  
Inhibitory Effects ◽  
Primary Hepatocytes ◽  
Direct Role ◽  
Targeted Inhibition ◽  
Dependent Mechanism

Dicer processes microRNAs (miRs) into active forms in a wide variety of tissues, including the liver. To determine the role of Dicer in liver regeneration, we performed a series of in vivo and in vitro studies in a murine 2/3 hepatectomy model. Dicer was downregulated after 2/3 hepatectomy, and loss of Dicer inhibited liver regeneration associated with decreased cyclin A2 and miR-221, as well as increased levels of the cell cycle inhibitor p27. In vitro, miR-221 inhibited p27 production in primary hepatocytes and increased hepatocyte proliferation. Specific reconstitution of miR-221 in hepatocyte-specific Dicer-null mice inhibited p27 and restored liver regeneration. In wild type mice, targeted inhibition of miR-221 using a cholesterol-conjugated miR-221 inhibited hepatocyte proliferation after 2/3 hepatectomy. These results identify Dicer production of miR-221 as an essential component of a miRNA-dependent mechanism for suppression of p27 that controls the rate of hepatocyte proliferation after partial hepatectomy. NEW & NOTEWORTHY Our findings demonstrate a direct role for microRNAs in controlling the rate of liver regeneration after injury. By deleting Dicer, an enzyme responsible for processing microRNAs into mature forms, we determined miR-221 is a critical microRNA in the physiological process of restoration of liver mass after injury. miR-221 suppresses p27, releasing its inhibitory effects on hepatocyte proliferation. Pharmaceuticals based on miR-221 may be useful to modulate hepatocyte proliferation in the setting of liver injury.

scholarly journals F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2231
Author(s):  
Qingjun Lu ◽  
Hao Shen ◽  
Han Yu ◽  
Jing Fu ◽  
Hui Dong ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Regenerative Process ◽  
Oncostatin M ◽  
Hepatocyte Proliferation ◽  
Initiation Phase ◽  
Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

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