Changes in COX-2 and oxidative damage factors during differentiation of human mesenchymal stem cells to hepatocyte-like cells is associated with downregulation of P53 gene
Abstract
Differentiation of human mesenchymal stem cells (MSCs) to metabolically active hepatocytes depends on different regulatory factors. Trans-differentiation of stem cells into specific cell lineage in the presence of specific stimuli is associated with the molecular and cellular damage. The aim of the present study was to examine the role of P53 in the regulation of cyclooxygenase-2 (COX-2) expression and the generation of protein and lipid oxidation during trans-differentiation of MSCs into hepatocyte-like cells. During the 3-week differentiation process of MSCs to hepatocyte-like cells we found that expression liver-specific markers was associated with increased levels of lipid peroxidation and protein carbonyl formation. Expression of P53 and COX-2 at mRNA and protein levels were evaluated in MSCs before and after differentiation on days 7, 14 and 21. We showed that the up-regulation of COX-2 was associated with augmentation of the rate of cell proliferation, morphological and biochemical changes of hepatocytes-like cells. However, in parallel the P53 at the mRNA level was down-regulated, and at protein levels accumulation in the nuclei was reduced during the hepatogenic differentiation time. Our results may suggest a P53-COX-2 pathway in the regulation of hepatogenic differentiation of stem cells, which is linked to differentiation-dependent molecular oxidative damage.
This study was supported by a grant (Grant # 90007389) provided by Iran National Science Foundation (INSF). Safoura Khajeniazi is currently a PhD student at the faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran and this paper is part of her PhD dissertation.
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Articles in the same Issue
- Masthead
- Masthead
- Reviews
- Imaging the invisible: resolving cellular microcompartments by superresolution microscopy techniques
- Structure and function of MK5/PRAK: the loner among the mitogen-activated protein kinase-activated protein kinases
- Functional ribosome biogenesis is a prerequisite for p53 destabilization: impact of chemotherapy on nucleolar functions and RNA metabolism
- Interleukin-6 and interleukin-11: same same but different
- Cathepsin K: a unique collagenolytic cysteine peptidase
- Research Articles/Short Communications
- Protein Structure and Function
- The active form of goat insulin-like peptide 3 (INSL3) is a single-chain structure comprising three domains B-C-A, constitutively expressed and secreted by testicular Leydig cells
- Molecular Medicine
- Zinc-dependent contact system activation induces vascular leakage and hypotension in rodents
- Cell Biology and Signaling
- ACE inhibition enhances bradykinin relaxations through nitric oxide and B1 receptor activation in bovine coronary arteries
- Changes in COX-2 and oxidative damage factors during differentiation of human mesenchymal stem cells to hepatocyte-like cells is associated with downregulation of P53 gene
- Overexpression of miR-126 promotes the differentiation of mesenchymal stem cells toward endothelial cells via activation of PI3K/Akt and MAPK/ERK pathways and release of paracrine factors
- Novel Techniques
- Synthesis of a novel benzodifuran derivative and its molecular recognition of poly rA RNA
Articles in the same Issue
- Masthead
- Masthead
- Reviews
- Imaging the invisible: resolving cellular microcompartments by superresolution microscopy techniques
- Structure and function of MK5/PRAK: the loner among the mitogen-activated protein kinase-activated protein kinases
- Functional ribosome biogenesis is a prerequisite for p53 destabilization: impact of chemotherapy on nucleolar functions and RNA metabolism
- Interleukin-6 and interleukin-11: same same but different
- Cathepsin K: a unique collagenolytic cysteine peptidase
- Research Articles/Short Communications
- Protein Structure and Function
- The active form of goat insulin-like peptide 3 (INSL3) is a single-chain structure comprising three domains B-C-A, constitutively expressed and secreted by testicular Leydig cells
- Molecular Medicine
- Zinc-dependent contact system activation induces vascular leakage and hypotension in rodents
- Cell Biology and Signaling
- ACE inhibition enhances bradykinin relaxations through nitric oxide and B1 receptor activation in bovine coronary arteries
- Changes in COX-2 and oxidative damage factors during differentiation of human mesenchymal stem cells to hepatocyte-like cells is associated with downregulation of P53 gene
- Overexpression of miR-126 promotes the differentiation of mesenchymal stem cells toward endothelial cells via activation of PI3K/Akt and MAPK/ERK pathways and release of paracrine factors
- Novel Techniques
- Synthesis of a novel benzodifuran derivative and its molecular recognition of poly rA RNA