Deceleration of regenerative response improves the outcome of rat with massive hepatectomy

M. Ninomiya, K. Shirabe, T. Terashi, H. Ijichi, Y. Yonemura, N. Harada, Y. Soejima, A. Taketomi, M. Shimada, Y. Maehara

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Small residual liver volume after massive hepatectomy or partial liver transplantation is a major cause of subsequent liver dysfunction. We hypothesize that the abrupt regenerative response of small remnant liver is responsible for subsequent deleterious outcome. To slow down the regenerative speed, NS-398 (ERK1/2 inhibitor) or PD98059 (selective MEK inhibitor) was administered after 70% or 90% partial hepatectomy (PH). The effects of regenerative speed on liver morphology, portal pressure and survival were assessed. In the 70% PH model, NS-398 treatment suppressed the abrupt replicative response of hepatocytes during the early phase of regeneration, although liver volume on day 7 was not significantly different from that of the control group. Immunohistochemical analysis for CD31 (for sinusoids) and AGp110 (for bile canaliculi) revealed that lobular architectural disturbance was alleviated by NS-398 treatment. In the 90% PH model, administration of NS-398 or PD98059, but not hepatocyte growth factor, significantly enhanced survival. The abrupt regenerative response of small remnant liver is suggested to be responsible for intensive lobular derangement and subsequent liver dysfunction. The suppression of MEK/ERK signaling pathway during the early phase after hepatectomy makes the regenerative response linear, and improves the prognosis for animals bearing a small remnant liver.

Original languageEnglish
Pages (from-to)1580-1587
Number of pages8
JournalAmerican Journal of Transplantation
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 1 2010

Fingerprint

Deceleration
Hepatectomy
Liver
Liver Diseases
Bile Canaliculi
Portal Pressure
Liver Regeneration
Residual Volume
Hepatocyte Growth Factor
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
Liver Transplantation
Hepatocytes
Control Groups
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Deceleration of regenerative response improves the outcome of rat with massive hepatectomy. / Ninomiya, M.; Shirabe, K.; Terashi, T.; Ijichi, H.; Yonemura, Y.; Harada, N.; Soejima, Y.; Taketomi, A.; Shimada, M.; Maehara, Y.

In: American Journal of Transplantation, Vol. 10, No. 7, 01.07.2010, p. 1580-1587.

Research output: Contribution to journalArticle

Ninomiya, M, Shirabe, K, Terashi, T, Ijichi, H, Yonemura, Y, Harada, N, Soejima, Y, Taketomi, A, Shimada, M & Maehara, Y 2010, 'Deceleration of regenerative response improves the outcome of rat with massive hepatectomy', American Journal of Transplantation, vol. 10, no. 7, pp. 1580-1587. https://doi.org/10.1111/j.1600-6143.2010.03150.x
Ninomiya, M. ; Shirabe, K. ; Terashi, T. ; Ijichi, H. ; Yonemura, Y. ; Harada, N. ; Soejima, Y. ; Taketomi, A. ; Shimada, M. ; Maehara, Y. / Deceleration of regenerative response improves the outcome of rat with massive hepatectomy. In: American Journal of Transplantation. 2010 ; Vol. 10, No. 7. pp. 1580-1587.
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