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Increased sinusoidal flow is not the primary stimulus to liver regeneration.

Mortensen KE, Conley LN, Nygaard I, Sorenesen P, Mortensen E, Bendixen C, Revhaug A - Comp Hepatol (2010)

Bottom Line: Gene expression profiling from the shunted segments does not suggest that increased sinusoidal flow per se results in activation of genes promoting mitosis.Hyperperfusion over three weeks results in the whole liver gaining a supranormal weight of 3.9% of the total body weight (versus the normal 2.5%).Contrary to our hypothesis, the weight gain was observed on the non-shunted side without an increase in sinusoidal flow.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgical Research Laboratory, Institute of Clinical Medicine, University of Tromsoe, Tromsoe, Norway.

ABSTRACT

Background: Hemodynamic changes in the liver remnant following partial hepatectomy (PHx) have been suggested to be a primary stimulus in triggering liver regeneration. We hypothesized that it is the increased sinusoidal flow per se and hence the shear-stress stimulus on the endothelial surface within the liver remnant which is the main stimulus to regeneration. In order to test this hypothesis we wanted to increase the sinusoidal flow without performing a concomitant liver resection. Accordingly, we constructed an aorto-portal shunt to the left portal vein branch creating a standardized four-fold increase in flow to segments II, III and IV. The impact of this manipulation was studied in both an acute model (6 animals, 9 hours) using a global porcine cDNA microarray chip and in a chronic model observing weight and histological changes (7 animals, 3 weeks).

Results: Gene expression profiling from the shunted segments does not suggest that increased sinusoidal flow per se results in activation of genes promoting mitosis. Hyperperfusion over three weeks results in the whole liver gaining a supranormal weight of 3.9% of the total body weight (versus the normal 2.5%). Contrary to our hypothesis, the weight gain was observed on the non-shunted side without an increase in sinusoidal flow.

Conclusions: An isolated increase in sinusoidal flow does not have the same genetic, microscopic or macroscopic impact on the liver as that seen in the liver remnant after partial hepatectomy, indicating that increased sinusoidal flow may not be a sufficient stimulus in itself for the initiation of liver regeneration.

No MeSH data available.


Related in: MedlinePlus

Functional distribution of differentially expressed genes. Illustration of differentially expressed genes at given time points sorted by genetic function according to Gene Ontology in the shunted and sham pigs (contrasts within time points).
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Figure 4: Functional distribution of differentially expressed genes. Illustration of differentially expressed genes at given time points sorted by genetic function according to Gene Ontology in the shunted and sham pigs (contrasts within time points).

Mentions: By analyzing differences between the shunt and sham groups at individual sampling time points and examining potential functions of the gene products by categorization according to cellular process and molecular function (Gene Ontology) we found that in terms of genetic function, although there were many genes whose expression differed in the two groups at each time point of sampling after shunt opening and sham surgery, the functional distribution of the potential gene products were similar in both groups. However, there were far more genes differentially expressed in the sham group (Fig. 4).


Increased sinusoidal flow is not the primary stimulus to liver regeneration.

Mortensen KE, Conley LN, Nygaard I, Sorenesen P, Mortensen E, Bendixen C, Revhaug A - Comp Hepatol (2010)

Functional distribution of differentially expressed genes. Illustration of differentially expressed genes at given time points sorted by genetic function according to Gene Ontology in the shunted and sham pigs (contrasts within time points).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2819042&req=5

Figure 4: Functional distribution of differentially expressed genes. Illustration of differentially expressed genes at given time points sorted by genetic function according to Gene Ontology in the shunted and sham pigs (contrasts within time points).
Mentions: By analyzing differences between the shunt and sham groups at individual sampling time points and examining potential functions of the gene products by categorization according to cellular process and molecular function (Gene Ontology) we found that in terms of genetic function, although there were many genes whose expression differed in the two groups at each time point of sampling after shunt opening and sham surgery, the functional distribution of the potential gene products were similar in both groups. However, there were far more genes differentially expressed in the sham group (Fig. 4).

Bottom Line: Gene expression profiling from the shunted segments does not suggest that increased sinusoidal flow per se results in activation of genes promoting mitosis.Hyperperfusion over three weeks results in the whole liver gaining a supranormal weight of 3.9% of the total body weight (versus the normal 2.5%).Contrary to our hypothesis, the weight gain was observed on the non-shunted side without an increase in sinusoidal flow.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgical Research Laboratory, Institute of Clinical Medicine, University of Tromsoe, Tromsoe, Norway.

ABSTRACT

Background: Hemodynamic changes in the liver remnant following partial hepatectomy (PHx) have been suggested to be a primary stimulus in triggering liver regeneration. We hypothesized that it is the increased sinusoidal flow per se and hence the shear-stress stimulus on the endothelial surface within the liver remnant which is the main stimulus to regeneration. In order to test this hypothesis we wanted to increase the sinusoidal flow without performing a concomitant liver resection. Accordingly, we constructed an aorto-portal shunt to the left portal vein branch creating a standardized four-fold increase in flow to segments II, III and IV. The impact of this manipulation was studied in both an acute model (6 animals, 9 hours) using a global porcine cDNA microarray chip and in a chronic model observing weight and histological changes (7 animals, 3 weeks).

Results: Gene expression profiling from the shunted segments does not suggest that increased sinusoidal flow per se results in activation of genes promoting mitosis. Hyperperfusion over three weeks results in the whole liver gaining a supranormal weight of 3.9% of the total body weight (versus the normal 2.5%). Contrary to our hypothesis, the weight gain was observed on the non-shunted side without an increase in sinusoidal flow.

Conclusions: An isolated increase in sinusoidal flow does not have the same genetic, microscopic or macroscopic impact on the liver as that seen in the liver remnant after partial hepatectomy, indicating that increased sinusoidal flow may not be a sufficient stimulus in itself for the initiation of liver regeneration.

No MeSH data available.


Related in: MedlinePlus