FAK deletion accelerates liver regeneration after two-thirds partial hepatectomy

Shang, Na; Arteaga, Maribel; Chitsike, Lennox; Wang, Fang; Viswakarma, Navin; Breslin, Peter; Qiu, Wei

doi:10.1038/srep34316

Cited by 12 publications

(10 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, cell migration is a critical process in tissue formation, such as wound healing (Aragona et al, ). In the hepatic fibrosis, hepatocytes migration plays an important role in the liver regeneration (Shang et al, ,). It is also an important embodiment of the cell's mechanical properties.…”

Section: Discussionmentioning

confidence: 99%

Effect of substrate stiffness on hepatocyte migration and cellular Young's modulus

Xia

Zhao

Liu

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Hepatic fibrosis progress accompanied by an unbalanced extracellular matrix (ECM) degradation and deposition leads to an increased tissue stiffness. Hepatocytes interplay with all intrahepatic cell populations inside the liver. However, how hepatocytes migration and cellular Young's modulus influenced by the substrate stiffness are not well understood. Here, we established a stiffness-controllable in vitro cell culture model by using a polyvinyl alcohol (PVA) hydrogel that mimicked the same physical stiffness as a fibrotic liver. Three levels of stiffness were used in our experiment that corresponded to the stiffness levels found in normal liver tissue (4.5 kPa), the early (19 kPa) and late stages (37 kPa) of fibrotic liver tissues. Cytoskeleton of hepatocyte was influenced by substrate stiffness. Soft substrate promoted the cellular migration and directionality. The cellular Young's modulus firstly increased and then decreased with increasing substrate stiffness. Integrin-β1 and β-catenin expression on cytomembrane were up-regulated and down-regulated with the increase of substrate stiffness, respectively. Our data not only suggested that hepatocytes were sensitive to substrate stiffness, but also suggested that there may be a potential relationship among substrate stiffness, cellular Young's modulus and the dynamic balance of integrin-β1 and β-catenin pathways. These results may provide us a new insight in mechanism investigation of mechano-dependent diseases, especially like fibrosis related diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of substrate stiffness on hepatocyte migration and cellular Young's modulus

Xia

Zhao

Liu

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Western blotting was performed as described 19, 25. Primary antibodies, including those for IGF1R, phosphorylated IGF1R, caspase‐3, active caspase‐3, poly(adenosine diphosphate ribose) polymerase, phosphorylated (p‐)AKT (ser473), AKT, p‐extracellular signal‐regulated kinase (ERK), and ERK, were purchased from Cell Signaling Technology (Danvers, MA).…”

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry was performed as described 25. Detailed antibody information can be found in Table 2.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of insulin‐like growth factor 1 receptor enhances the efficacy of sorafenib in inhibiting hepatocellular carcinoma cell growth and survival

Wang

Bank

Malnassy

et al. 2018

Hepatology Communications

Self Cite

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the fifth most common primary cancer and second largest cause of cancer‐related death worldwide. The first‐line oral chemotherapeutic agent sorafenib only increases survival in patients with advanced HCC by less than 3 months. Most patients with advanced HCC have shown limited response rates and survival benefits with sorafenib. Although sorafenib is an inhibitor of multiple kinases, including serine/threonine‐protein kinase c‐Raf, serine/threonine‐protein kinase B‐Raf, vascular endothelial growth factor receptor (VEGFR)‐1, VEGFR‐2, VEGFR‐3, and platelet‐derived growth factor receptor β, HCC cells are able to escape from sorafenib treatment using other pathways that the drug insufficiently inhibits. The aim of this study was to identify and target survival and proliferation pathways that enable HCC to escape the antitumor activity of sorafenib. We found that insulin‐like growth factor 1 receptor (IGF1R) remains activated in HCC cells treated with sorafenib. Knockdown of IGF1R sensitizes HCC cells to sorafenib treatment and decreases protein kinase B (AKT) activation. Overexpression of constitutively activated AKT reverses the effect of knockdown of IGF1R in sensitizing HCC cells to treatment with sorafenib. Further, we found that ceritinib, a drug approved by the U.S. Food and Drug Administration for treatment of non‐small cell lung cancer, effectively inhibits the IGF1R/AKT pathway and enhances the inhibitory efficacy of sorafenib in human HCC cell growth and survival in vitro, in a xenograft mouse model and in the c‐Met/β‐catenin‐driven HCC mouse model. Conclusion: Our study provides a biochemical basis for evaluation of a new combination treatment that includes IGF1R inhibitors, such as ceritinib and sorafenib, in patients with HCC. (Hepatology Communications 2018;2:732‐746)

show abstract

“…Since human adipokines have not yet been completely characterized (i.e., there are more than 600 potential adipokines unidentified) [ 83 ], several studies have been reported to selectively examine the precise function of every single adipokine through KO models. Indeed, many authors used knockout (KO) mice in the last five years, using 70% PH without vascular occlusion [ 23 , 24 , 52 , 64 , 66 , 73 ]. However, no one of the studies mentioned has evaluated the gene-specific null mutations of adipokines in steatotic livers, which represents a limitation to transfer to the bedside.…”

Section: The Animal Models Of Phmentioning

confidence: 99%

The Role of Adipokines in Surgical Procedures Requiring Both Liver Regeneration and Vascular Occlusion

Álvarez‐Mercado

Bujaldon

Gracia‐Sancho

et al. 2018

IJMS

View full text Add to dashboard Cite

Liver regeneration is a perfectly calibrated mechanism crucial to increase mass recovery of small size grafts from living donor liver transplantation, as well as in other surgical procedures including hepatic resections and liver transplantation from cadaveric donors. Regeneration involves multiple events and pathways in which several adipokines contribute to their orchestration and drive hepatocytes to proliferate. In addition, ischemia-reperfusion injury is a critical factor in hepatic resection and liver transplantation associated with liver failure or graft dysfunction post-surgery. This review aims to summarize the existing knowledge in the role of adipokines in surgical procedures requiring both liver regeneration and vascular occlusion, which increases ischemia-reperfusion injury and regenerative failure. We expose and discuss results in small-for-size liver transplantation and hepatic resections from animal studies focused on the modulation of the main adipokines associated with liver diseases and/or regeneration published in the last five years and analyze future perspectives and their applicability as potential targets to decrease ischemia-reperfusion injury and improve regeneration highlighting marginal states such as steatosis. In our view, adipokines means a promising approach to translate to the bedside to improve the recovery of patients subjected to partial hepatectomy and to increase the availability of organs for transplantation.

show abstract

FAK deletion accelerates liver regeneration after two-thirds partial hepatectomy

Cited by 12 publications

References 45 publications

Effect of substrate stiffness on hepatocyte migration and cellular Young's modulus

Effect of substrate stiffness on hepatocyte migration and cellular Young's modulus

Inhibition of insulin‐like growth factor 1 receptor enhances the efficacy of sorafenib in inhibiting hepatocellular carcinoma cell growth and survival

The Role of Adipokines in Surgical Procedures Requiring Both Liver Regeneration and Vascular Occlusion

Contact Info

Product

Resources

About