Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy

An, Shucai; Soe, Kyaw; Akamatsu, Maki; Hishikawa, Yoshitaka; Koji, Takehiko

doi:10.1007/s00418-012-0994-4

Cited by 14 publications

(16 citation statements)

References 44 publications

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“…Thus, enhanced vulnerability of the livers to surgical insult is unlikely to be a prima facie cause of hepatocyte proliferation inhibition by hepcidin. Recently, An et al [20] demonstrated that chronic iron overload accelerates liver regeneration in rats after PH, probably due to the shortening of the G0-G1 transition. Since hepcidin reduces the levels of serum iron, the limitation of iron availability by overexpressing hepcidin is probably harmful to the cell cycle of the hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Hepcidin plays a negative role in liver regeneration

Wang¹,

Gao²,

Yang³

et al. 2013

ABBS

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Hepcidin is a key regulator of iron metabolism. The expression of hepcidin is significantly induced by iron overload, inflammation, and infection of pathogens. Recent studies have indicated that the expression of hepcidin in the liver is also regulated during liver regeneration. However, the mechanism of the regulation of hepcidin expression and its role in liver regeneration remain unclear. In this study, we found that the hepatocyte growth factor inhibited hepcidin expression in the liver during the late stage of liver regeneration. Meanwhile, we investigated the effect of hepcidin on liver regeneration. Mice overexpressing hepcidin-1 exhibited impaired hepatic regeneration after partial hepatectomy, as determined by immunohistochemical staining of the proliferation cell nuclear antigen. Our results demonstrated a negative role of hepcidin in modulating liver regeneration, and suggested that a sustained high iron level by the down-regulation of hepcidin at the late stage of liver regeneration is required for hepatocyte proliferation.

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Section: Discussionmentioning

confidence: 99%

Hepcidin plays a negative role in liver regeneration

Wang¹,

Gao²,

Yang³

et al. 2013

ABBS

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“…In another study [34], iron deposition was found in 43% of the HCC cases and indicated that, in Myanmar patients with HCC, iron deposition might accelerate hepatocarcinogenesis, by promoting cancer cell proliferation, without affecting the Fas/FasL apoptotic system. A recently study [35] showed that chronic iron overload seemed to induce nuclear localization of MT and NF-jB activation, with a resultant marked acceleration of liver regeneration in ironoverload rats after PH occurring at least 12 h earlier than that in normal-diet rats. The accelerated liver regeneration was likely due to the shortening of G0–G1 transition, possibly by bypassing the signaling cascades required for the induction of hepatocyte proliferation.…”

Section: Discussionmentioning

confidence: 99%

Geographic patterns of hepatocellular carcinoma mortality with exposure to iron in groundwater in Taiwanese population: An ecological study

Shyu

Lung

et al. 2013

BMC Public Health

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BackgroundMany studies have examined the risk factors for HCC (including hepatitis B virus, hepatitis C virus, aflatoxin, retinol, cigarette smoking, and alcohol consumption). However, data from previous studies on the association between iron exposure, land subsidence, and HCC mortality/incidence were limited, especially in Taiwanese population. We aimed to explore the geographical distribution of HCC mortality rates by township-specific data and to evaluate the association between HCC mortality, land subsidence, and iron levels in groundwater in Taiwan.MethodsWe conducted an ecological study and calculated the HCC age-standardized mortality/incidence rates according to death certificates issued in Taiwan from 1992 to 2001 and incidence data from 1995–1998. The land subsidence dataset before 2005 and iron concentrations in groundwater in 1989 are also involved in this study. Both geographical information systems and Pearson correlation coefficients were used to analyze the relationship between HCC mortality rates, land subsidence, and iron concentrations in groundwater.ResultsTownship-specific HCC mortality rates are higher in southwestern coastal townships where serious land subsidence and higher township-specific concentrations of iron in groundwater are present. The Pearson correlation coefficients of iron concentrations in groundwater and ASRs of HCC were 0.286 (P = 0.004) in males and 0.192 (P = 0.058) in females for mortality data; the coefficients were 0.375 (P < 0.001) in males and 0.210 (P = 0.038) in females for incidence data.ConclusionsThis study showed that HCC mortality is clustered in southwestern Taiwan and the association with the iron levels in groundwater in Taiwanese population warrant further investigation.

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“…Immunohistochemistry was performed to determine the expression of KGF and KGFR in tissue sections using anti-KGF and anti-KGFR antibodies as previously described [2, 15, 22, 26]. Sections of rat lung tissue were deparaffinized and those for KGFR expression were pretreated with 0.2% Triton X-100 in PBS for 15 min at RT.…”

Section: Methodsmentioning

confidence: 99%

“…To analyze internucleosomal DNA fragmentation as a hallmark of apoptosis, TUNEL was performed as previously described [2, 3]. The sections were reacted with 200 U/ml TdT (Roche, Munich, Germany) dissolved in TdT buffer (25 mM Tris/HCl buffer, pH 6.6, containing 0.2 M potassium cacodylate and 0.25 mg/ml BSA) (Roche, Munich, Germany) supplemented with 0.5 µM biotin-16-dUTP, 20 µM dATP, 1.5 mM CoCl 2 , and 0.1 mM dithiothreitol for 90 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat

Furukawa

Matsumoto

Nagayasu

et al. 2013

Acta Histochem. Cytochem

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Keratinocyte growth factor (KGF) is considered to be one of the most important mitogens for lung epithelial cells. The objectives of this study were to confirm the effectiveness of intratracheal injection of recombinant human KGF (rhKGF) during compensatory lung growth and to optimize the instillation protocol. Here, trilobectomy in adult rat was performed, followed by intratracheal rhKGF instillation with low (0.4 mg/kg) and high (4 mg/kg) doses at various time-points. The proliferation of alveolar cells was assessed by the immunostaining for proliferating cell nuclear antigen (PCNA) in the residual lung. We also investigated other immunohistochemical parameters such as KGF, KGF receptor and surfactant protein A as well as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Consequently, intratracheal single injection of rhKGF in high dose group significantly increased PCNA labeling index (LI) of alveolar cells in the remaining lung. Surprisingly, there was no difference in PCNA LI between low and high doses of rhKGF with daily injection, and PCNA LI reached a plateau level with 2 days-consecutive administration (about 60%). Our results indicate that even at low dose, daily intratracheal injection is effective to maintain high proliferative states during the early phase of compensatory lung growth.

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Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy

Cited by 14 publications

References 44 publications

Hepcidin plays a negative role in liver regeneration

Hepcidin plays a negative role in liver regeneration

Geographic patterns of hepatocellular carcinoma mortality with exposure to iron in groundwater in Taiwanese population: An ecological study

Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat

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