Bone marrow-derived mesenchymal stem cells utilize the notch signaling pathway to induce apoptosis of hepatic stellate cells via NF-κB sensor
Abstract
The present study aimed at evaluating the mechanism by which functionality of hepatic stellate cells (HSCs) is modulated by bone marrow stromal cells (BMSCs). Induction of apoptosis in HSCs was found to be caused by directly co-culturing HSCs with BMSCs, where the expression of α-smooth muscle actin (α-SMA) increased significantly in HSCs, along with an increase in their proliferation rate. Additionally, expression of Hes1 and Notch1 in HSCs co-cultured with BMSCs increased significantly at both protein and mRNA levels. Blocking of the notch signaling pathway (NSP) either by Notch1 siRNA or by DAPT treatment increased the proliferation rate while decreasing apoptosis and led to activation of the NF-κB signaling pathway in HSCs co-cultured with BMSCs. These effects were found to be reversed in HSCs overexpressing IκB S32/S36 mutants. The Notch signaling-mediated cell-cell contact was partially involved in the significant inhibition of proliferation of HSCs by BMSCs. Additionally, the NF-κB pathway was found to be responsible for NSP-mediated inhibition of growth of HSCs in the co-culture system. Thus, BMSCs might have a potential therapeutic significance in treating hepatic fibrosis.
Acknowledgment
Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest statement: No potential conflict of interest is reported by the authors.
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Articles in the same Issue
- Frontmatter
- Reviews
- Aha-type co-chaperones: the alpha or the omega of the Hsp90 ATPase cycle?
- Developments in anticancer vaccination: budding new adjuvants
- The cGMP system: components and function
- Minireview
- Platelets as a ‘natural factory’ for growth factor production that sustains normal (and pathological) cell biology
- Research Articles/Short Communications
- Genes And Nucleic Acids
- Hsa-miR-6165 downregulates insulin-like growth factor-1 receptor (IGF-1R) expression and enhances apoptosis in SW480 cells
- Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs
- Molecular Medicine
- Aberrant mitochondrial bioenergetics in the cerebral cortex of the Fmr1 knockout mouse model of fragile X syndrome
- Cell Biology and Signaling
- Bone marrow-derived mesenchymal stem cells utilize the notch signaling pathway to induce apoptosis of hepatic stellate cells via NF-κB sensor
- Different signaling and functionality of Rac1 and Rac1b in the progression of lung adenocarcinoma