Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesenchymal tissues harbour stromal cells capable of multilineage differentiation. Here, we demonstrate the isolation of mesenchymal stem cells (MSC) from rat peritoneal adipose tissue capable of osteogenic and adipogenic differentiation. Under in vitro conditions favouring hepatocyte differentiation, these MSC gained characteristic functions of hepatocytes such as the capacity to synthesize urea or store glycogen. Hepatocyte-specific transcripts of dipeptidylpeptidase type IV (CD26), albumin, cytochrome P450 type 1A1 (CYP1A1) and connexin CX32 (CX32) were detected only in differentiated but not undifferentiated cells. Transient transgenic expression of luciferase could be stimulated by cAMP when driven by the hepatocyte-specific promoter of the cytosolic phosphoenolpyruvate carboxykinase (PCK1) gene. Finally, stem cell-derived hepatocytes from wild type (CD26+/+) rats were transplanted into the livers of CD26-deficient animals after lentiviral transduction with the GFP gene under the control of the ubiquitin promoter. GFP-positive cells engrafted in the host liver predominantly in the periportal region of the liver lobule. They continued to express CD26, a prominent feature of differentiated hepatocytes, indicating their topologically and functionally proper integration into the host liver parenchyma. Thus, MSCs from rat peritoneal adipose tissue exhibit the potential to differentiate into hepatocyte-like cells in vitro and in vivo.
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PMID:Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo. 1757 36

We developed previously a mouse voluntary climbing exercise model as a physiological mechanical loading model and reported that climbing exercise increased bone formation, but its effect on adipogenesis is unknown. We assessed the effects of loading and PTH/PTHrP receptor (PTHR1) on bone marrow adipocyte differentiation in relation with osteoblast differentiation. 8-week-old C57BL/6J male mice were divided into ground control (GC) and climbing exercise (EX) group. Mice were housed in 100-cm towers and climbed up toward a bottle placed at the top of the cage to drink water. The values of bone volume and osteoblast number were significantly higher while those of marrow adipocyte volume and number were significantly lower in the 28dayEX group than 28dayGC group. The mRNA expression levels of adipocyte differentiation genes CCAAT/enhancer-binding proteins (C/EBP) beta and delta were lower in 4dayEX mice, while the adipocyte specific genes fatty acid binding protein (aP2) and phosphoenolpyruvate carboxykinase (PEPCK) expressions were lower in 7dayEX mice. In primary bone marrow cell cultures, the number of alkaline phosphatase-positive colony forming units-fibroblastic (ALP+ CFU-f) and Oil-red-O-positive cells were both increased in the 4dayEX group. Climbing exercise transiently increases both osteogenic and adipogenic potential in bone marrow stromal cells, and inhibits terminal adipocyte differentiation and promotes osteoblast differentiation. Immunoreactivity for the PTHR1 was intense on osteoblastic cell lineage in the endosteal tibial metaphysis. PTHR1 mRNA expression was increased in 4dayEX mice and PTHR1-positive cells were increased after 7 days in the experimental group. Ex vivo addition of PTHR1 antibody decreased and that of PTHrP(1-34) increased the number of ALP+ CFU-f in bone marrow cell cultures obtained at 4 days after the exercise, while the addition of PTHR1 antibody increased and PTHrP(1-34) decreased the number of Oil-red-O-positive cells. Our results indicate that climbing exercise enhanced osteoblast differentiation and inhibited terminal differentiation of adipocyte progenitors with high expression of PTHR1 in bone marrow cells.
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PMID:Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells. 1856 52

Mitochondrial phosphoenolpyruvate carboxykinase (PCK2) is a rate-limiting enzyme that plays critical roles in multiple physiological processes. The decompensation of PCK2 leads to various energy metabolic disorders. However, little is known regarding the effects of PCK2 on osteogenesis by human mesenchymal stem cells (hMSCs). Here, we report a novel function of PCK2 as a positive regulator of MSCs osteogenic differentiation. In addition to its well-known role in anabolism, we demonstrate that PCK2 regulates autophagy. PCK2 deficiency significantly suppressed autophagy, leading to the impairment of osteogenic capacity of MSCs. On the other hand, autophagy was promoted by PCK2 overexpression; this was accompanied by increased osteogenic differentiation of MSCs. Moreover, PCK2 regulated osteogenic differentiation of MSCs via AMP-activated protein kinase (AMPK)/unc-51 like autophagy activating kinase 1(ULK1)-dependent autophagy. Collectively, our present study unveiled a novel role for PCK2 in integrating autophagy and bone formation, providing a potential target for stem cell-based bone tissue engineering that may lead to improved therapies for metabolic bone diseases. Stem Cells 2019;37:1542-1555.
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PMID:Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1-Dependent Autophagy. 3157 89