Effects of selective bile duct ligation on liver parenchyma in young animals: histologic and molecular evaluations

Tannuri, Ana Cristina Aoun; Coelho, Maria Cecília Mendonça; Gonçalves, Josiane de Oliveira; Santos, Marcela de Souza; Silva, Luiz Fernando Ferraz da; Bendit, Israel; Tannuri, Uenis

doi:10.1016/j.jpedsurg.2011.10.009

Cited by 16 publications

(26 citation statements)

References 25 publications

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“…It is possible that these branches are forced to extrude from the portal tract and invade the liver parenchyma. Chronic cholestasis eventually leads to fibrosis, which manifests itself as collagen‐filled “fibrotic streaks” that invade the parenchyma and interconnect portal tracts . Such ductular invasion of the liver parenchyma has been reported when hepatocyte regeneration is impaired following chemical injury, presumably “delivering” hepatic progenitors to the parenchyma through small penetrating bile ducts .…”

Section: Resultsmentioning

confidence: 99%

“…Chronic cholestasis eventually leads to fibrosis, which manifests itself as collagen-filled "fibrotic streaks" that invade the parenchyma and interconnect portal tracts. (16) Such ductular invasion of the liver parenchyma has been reported when hepatocyte regeneration is impaired following chemical injury, presumably "delivering" hepatic progenitors to the parenchyma through small penetrating bile ducts. (3,4,17) We therefore investigated whether the excess ductular tissue penetrates the liver parenchyma by measuring the pixel-wise distance between bile ducts and the portal vein.…”

Section: Mechanistic Restraints In Remodeling Of the Biliary Treementioning

confidence: 99%

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Cholestasis‐induced adaptive remodeling of interlobular bile ducts

et al. 2016

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Cholestasis is a common complication in liver diseases that triggers a proliferative response of the biliary tree. Bile duct ligation (BDL) is a frequently used model of cholestasis in rodents. To determine which changes occur in the three‐dimensional (3D) architecture of the interlobular bile duct during cholestasis, we used 3D confocal imaging, surface reconstructions, and automated image quantification covering a period up to 28 days after BDL. We show a highly reproducible sequence of interlobular duct remodeling, where cholangiocyte proliferation initially causes corrugation of the luminal duct surface, leading to an approximately five‐fold increase in surface area. This is analogous to the function of villi in the intestine or sulci in the brain, where an expansion of area is achieved within a restricted volume. The increase in surface area is further enhanced by duct branching, branch elongation, and loop formation through self‐joining, whereby an initially relatively sparse mesh surrounding the portal vein becomes five‐fold denser through elongation, corrugation, and ramification. The number of connections between the bile duct and the lobular bile canalicular network by the canals of Hering decreases proportionally to the increase in bile duct length, suggesting that no novel connections are established. The diameter of the interlobular bile duct remains constant after BDL, a response that is qualitatively distinct from that of large bile ducts, which tend to enlarge their diameters. Therefore, volume enhancement is only due to net elongation of the ducts. Because curvature and tortuosity of the bile duct are unaltered, this enlargement of the biliary tree is caused by branching and not by convolution. Conclusion: BDL causes adaptive remodeling that aims at optimizing the intraluminal surface area by way of corrugation and branching. (Hepatology 2016;63:951–964)

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Section: Resultsmentioning

confidence: 99%

Section: Mechanistic Restraints In Remodeling Of the Biliary Treementioning

confidence: 99%

Cholestasis‐induced adaptive remodeling of interlobular bile ducts

et al. 2016

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“…The mechanisms leading to increased collagen production and liver parenchyma fibrosis are poorly understood ( 1 ). These phenomena are commonly observed in children with biliary atresia, in whom the evolution to biliary cirrhosis and hepatic failure creates a need for liver transplantation in the majority of patients, even after a successful Kasai portoenterostomy ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

“…In order to investigate this possibility, we developed a selective bile duct ligation model in weaning rats. In that model, we observed that biliary proliferation and portal fibrosis occurred in both the cholestatic and the unobstructed lobes of the liver in response to biliary obstruction ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamic expression of desmin, α-SMA and TGF-β1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats

Gonçalves¹,

Tannuri²,

Coelho³

et al. 2014

Braz J Med Biol Res

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We previously described a selective bile duct ligation model to elucidate the process of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary stenosis. Using this model, we identified changes in the expression of alpha smooth muscle actin (α-SMA) both in the obstructed parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin and TGF-β1, molecules known to be involved in hepatic fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of liver fibrosis in this experimental model are not fully understood. This study aimed to evaluate the molecular changes in an experimental model of selective bile duct ligation and to compare the gene expression changes observed in RT-PCR and in real-time quantitative PCR (qRT‐PCR). Twenty-eight Wistar rats of both sexes and weaning age (21-23 days old) were used. The rats were separated into groups that were assessed 7 or 60 days after selective biliary duct ligation. The expression of desmin, α-SMA and TGF-β1 was examined in tissue from hepatic parenchyma with biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO), using RT-PCR and qRT‐PCR. The results obtained in this study using these two methods were significantly different. The BO parenchyma had a more severe fibrogenic reaction, with increased α-SMA and TGF-β1 expression after 7 days. The WBO parenchyma presented a later, fibrotic response, with increased desmin expression 7 days after surgery and increased α-SMA 60 days after surgery. The qRT‐PCR technique was more sensitive to expression changes than the semiquantitative method.

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“…Após um período de 15 dias da desobstrução, as alterações metabólicas e bioquímicas não são completamente reestabelecidas(KONTOURAS et al, 1984). A ligadura do ducto de um único lóbulo também produz lesão hepática em outras regiões do fígado por meios parácrinos e endócrinos(TANNURI et al, 2012).A dimetilnitrosamina (DMN) é um composto hepatotóxico, mutagênico e carcinogênico, podendo ser absorvido por ingestão ou inalação, e levando a irritações oculares, na pele, no trato respiratório, e em períodos prolongados provoca lesão hepática e aparecimento de tumores(KHANNA;PURI, 1966). Causa grande taxa de mortalidade quando usado em altas doses; em baixas doses, não induz à cirrose de modo eficaz.…”

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<b>Avaliação da terapia celular utilizando células-tronco mesenquimais para o tratamento de cirrose hepática em ratos <i>Wistar</i></b>

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À minha orientadora, Graciela Conceição Pignatari, por todos os ensinamentos e confiança depositada em mim nesta longa etapa, e sobretudo pela paciência em me ensinar um pouco mais sobre a perseverança, a humildade e a convivência; À minha co-orientadora, Patrícia Cristina Baleeiro Beltrão Braga, por todo o carinho e conhecimento transmitido ao longo desses anos, e pela imensa vontade de ensinar; À minha ex-orientadora e amiga, Elizangela dos Anjos Silva, por toda a amizade, dedicação, confiança, e sobretudo por ser essa pessoa maravilhosa com um enorme desejo em ajudar ao próximo; A todos os amigos, colegas e ex-colegas do Laboratório de Células-Tronco, por todos os momentos vividos juntos, e por todo o apoio na aquisição desta vitória:

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Effects of selective bile duct ligation on liver parenchyma in young animals: histologic and molecular evaluations

Cited by 16 publications

References 25 publications

Cholestasis‐induced adaptive remodeling of interlobular bile ducts

Cholestasis‐induced adaptive remodeling of interlobular bile ducts

Dynamic expression of desmin, α-SMA and TGF-β1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats

<b>Avaliação da terapia celular utilizando células-tronco mesenquimais para o tratamento de cirrose hepática em ratos <i>Wistar</i></b>

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