Mesenchymal Stem Cells Enhance Liver Regeneration via Improving Lipid Accumulation and Hippo Signaling

Liu, Yang; Yang, Faji; Li, Jun; Wang, Jinglin; Wang, Xun; Zhang, Yuheng; Yuan, Xianwen; Zhu, Wei; Shi, Xiaolei

doi:10.1155/2018/7652359

Cited by 17 publications

(19 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The retention of exogenous BMSCs in ALI lung tissue is a prerequisite for tissue repair [23]. In agreement with our findings, enhanced recruitment of exogenous MSCs to the lung tissue in ALI mice compared with normal control mice was observed [24], and the accelerating effect of inhibition of the Hippo pathway on the migration of MSCs has been demonstrated recently in other studies [24, 25]. Currently, the regulatory mechanisms of MSC migration remain unclear.…”

Section: Discussionsupporting

confidence: 89%

Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

Liu

2019

Mediators of Inflammation

View full text Add to dashboard Cite

The pathophysiology of the acute lung injury (ALI) is characterized by the damage of alveolar epithelial cells, which can be repaired by exogenous bone marrow-derived mesenchymal stem cells (BMSCs). However, the migration and differentiation abilities of BMSCs are not sufficient for the purpose, and a new approach that could strengthen the repair effects of BMSCs in ALI still needs to be clarified. We have previously proved that in vitro large tumor suppressor kinase 2- (Lats2-) underexpressing BMSCs may enhance their tissue repair effects in ALI; thus, in the present study, we tried to explore whether Lats2-underexpressing BMSCs could rescue lipopolysaccharide- (LPS-) induced ALI in vivo. BMSCs from C57BL/6 mice transfected with Lats2-interfering lentivirus vector or lentivirus blank controls were transplanted intratracheally into LPS-induced ALI mice. The retention and differentiation of BMSCs in the lung were evaluated by in vivo imaging, immunofluorescence staining, and Western blotting. The lung edema and permeability were assessed by lung wet weight/body weight ratio (LWW/BW) and measurements of proteins in bronchoalveolar lavage fluid (BALF) using ELISA. Acute lung inflammation was measured by the cytokines in the lung homogenate and BALF using RT-qPCR and ELISA, respectively. Lung injury was evaluated by HE staining and lung injury scoring. Pulmonary fibrosis was evaluated by Picrosirius red staining, immunohistochemistry for α-SMA and TGF-β1, and hydroxyproline assay and RT-qPCR for Col1α1 and Col3α1. Lats2-mediated inhibition of the Hippo pathway increased the retention of BMSCs and their differentiation toward type II alveolar epithelial cells in the lung. Furthermore, Lats2-underexpressing BMSCs improved lung edema, permeability of the lung epithelium, and lung inflammation. Finally, Lats2-underexpressing BMSCs alleviated lung injury and early pulmonary fibrosis. Our studies suggest that underexpression of Lats2 could further enhance the repair effects of BMSCs against epithelial impair and the therapeutic potential of BMSCs in ALI mice.

show abstract

Section: Discussionsupporting

confidence: 89%

Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

Liu

2019

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…In this study, the upregulation of FAT/CD36 and hepatic fat accumulation were found in female rat livers after PHX. Multiple studies have reported that hepatic fat accumulation occurs from 24 to 48 hr after 70% PHX in rats [17, 21, 36], which is concomitant with hepatocellular proliferation [10, 39]. Our results revealed that female rat livers exhibit marked fat accumulation in regenerating liver that started from 6 hr and peaked at 24 hr after PHX, whereas fat accumulation in male rat livers started from 36 hr after PHX.…”

Section: Discussionsupporting

confidence: 49%

“…In general, glucose is the main energy source for cellular metabolism when it is sufficiently available. PHX is known to induce systemic metabolic changes, including hypoglycemia and glycogen depletion, and leads to a change to the use of fat as energy substrate [17, 22]. Therefore, hepatic fat accumulation during early liver regeneration is considered to be an important process that is closely linked to the liver regenerative process.…”

Section: Discussionmentioning

confidence: 99%

“…We previously reported that estrogen accelerates hepatocyte proliferation through ERα in female rats, and enhances liver regeneration compared to male rats after 70% partial hepatectomy (PHX) [3]. During liver regeneration, fatty acids and triglycerides are required for hepatocyte proliferation [16, 17, 22], while cholesterol acts as a structural lipid for new cell membrane formation [7, 18, 27]. Recent reports also suggest that the transient fat accumulation in hepatocyte after PHX is thought to be a critical energy source for liver regeneration [12, 15, 29, 37].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Effect of Estrogen on Hepatic Fat Accumulation during Early Phase of Liver Regeneration after Partial Hepatectomy in Rats

Srisowanna

Choijookhuu

Yano

et al. 2019

Acta Histochem. Cytochem

View full text Add to dashboard Cite

Fatty liver is common in men and post-menopausal women, suggesting that estrogen may be involved in liver lipid metabolism. The aim of this study is to be clear the role of estrogen and estrogen receptor alpha (ERα) in fat accumulation during liver regeneration using the 70% partial hepatectomy (PHX) model in male, female, ovariectomized (OVX) and E 2-treated OVX (OVX-E 2) rats. Liver tissues were sampled at 0-48 hr after PHX and fat accumulation, fatty acid translocase (FAT/CD36), sterol regulatory element-binding protein (SREBP1c), peroxisome proliferator-activated receptor α (PPARα), proliferative cell nuclear antigen (PCNA) and ERα were examined by Oil Red O, qRT-PCR and immunohistochemistry, respectively. Hepatic fat accumulation was abundant in female and OVX-E 2 compared to male and OVX rats. FAT/CD36 expression was observed in female, OVX and OVX-E 2 at 0-12 hr after PHX, but not in male rats. At 0 hr, SREBP1c and PPARα were elevated in female and male rats, respectively, but were decreased after PHX in all rats. The PCNA labeling index reached a maximum at 36 hr and 48 hr in OVX-E 2 and OVX rats, respectively. ERα expression in OVX-E 2 was higher than OVX at 0-36 hr after PHX. In conclusion, these results indicated that estrogen and ERα might play an important role in fat accumulation related to FAT/CD36 during early phase of rat liver regeneration.

show abstract

“…In addition, MSCs also improved liver regeneration and restored liver function in the PH model partly via mechanistic target of rapamycin (mTOR) signaling and improved lipid β-oxidation. In addition, MSCs further activated the STAT3 and Hippo-YAP pathways to improve hepatocyte proliferation for liver regeneration [56]. Preoperative resveratrol administration enhanced the homing capacity of MSCs into liver tissue, thus decreasing the expression of TNF-α and IL-6 and improving liver regeneration in PH-treated rats [57].…”

Section: Msc Transplantation Promotes Liver Regeneration In Partial Hmentioning

confidence: 99%

Mesenchymal stromal cells promote liver regeneration through regulation of immune cells

Wang

2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

The liver is sensitive to pathogen-induced acute or chronic liver injury, and liver transplantation (LT) is the only effective strategy for end-stage liver diseases. However, the clinical application is limited by a shortage of liver organs, immunological rejection and high cost. Mesenchymal stromal cell (MSC)-based therapy has gradually become a hot topic for promoting liver regeneration and repairing liver injury in various liver diseases, since MSCs are reported to migrate toward injured tissues, undergo hepatogenic differentiation, inhibit inflammatory factor release and enhance the proliferation of liver cells in vivo. MSCs exert immunoregulatory effects through cell-cell contact and the secretion of anti-inflammatory factors to inhibit liver inflammation and promote liver regeneration. In addition, MSCs are reported to effectively inhibit the activation of cells of the innate immune system, including macrophages, natural killer (NK) cells, dendritic cells (DCs), monocytes and other immune cells, and inhibit the activation of cells of the adaptive immune system, including T lymphocytes, B lymphocytes and subsets of T cells or B cells. In the current review, we mainly focus on the potential effects and mechanisms of MSCs in inhibiting the activation of immune cells to attenuate liver injury in models or patients with acute liver failure (ALF), nonalcoholic fatty liver disease (NAFLD), and liver fibrosis and in patients or models after LT. We highlight that MSC transplantation may replace general therapies for eliminating acute or chronic liver injury in the near future.

show abstract

Mesenchymal Stem Cells Enhance Liver Regeneration via Improving Lipid Accumulation and Hippo Signaling

Cited by 17 publications

References 37 publications

Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

Lats2-Underexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice

The Effect of Estrogen on Hepatic Fat Accumulation during Early Phase of Liver Regeneration after Partial Hepatectomy in Rats

Mesenchymal stromal cells promote liver regeneration through regulation of immune cells

Contact Info

Product

Resources

About