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Kidney ischemia/reperfusion injury causes cholangiocytes primary cilia disruption and abnormal bile secretion.
Han, Yong Kwon; Lim, Hui Jae; Jang, GiBong; Jang, Se Young; Park, Kwon Moo.
Afiliación
  • Han YK; Department of Anatomy, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea.
  • Lim HJ; Department of Anatomy, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea; Department of Biomedical Science and BK21 Plus, The Graduate School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic
  • Jang G; Department of Anatomy, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea; Department of Biomedical Science and BK21 Plus, The Graduate School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic
  • Jang SY; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea.
  • Park KM; Department of Anatomy, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea; Department of Biomedical Science and
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167225, 2024 08.
Article en En | MEDLINE | ID: mdl-38749218
ABSTRACT

BACKGROUND:

Acute kidney injury (AKI) causes distant liver injury, to date, which causes poor outcomes of patients with AKI. Many studies have been performed to overcome AKI-associated liver injury. However, those studies have mainly focused on hepatocytes, and AKI-induced liver injury still remains a clinical problem. Here, we investigated the implication of cholangiocytes and their primary cilia which are critical in final bile secretion. Cholangiocyte, a lining cell of bile ducts, are the only liver epithelial cell containing primary cilium (a microtubule-based cell surface signal-sensing organelle).

METHODS:

Cystathione γ-lyase (CSE, a transsulfuration enzyme) deficient and wild-type mice were subjected to kidney ischemia followed by reperfusion (KIR). Some mice were administered with N-acetyl-cysteine (NAC).

RESULTS:

KIR damaged hepatocytes and cholagiocytes, disrupted cholangiocytes primary cilia, released the disrupted ciliary fragments into the bile, and caused abnormal bile secretion. Glutathione (GSH) and H2S levels in the livers were significantly reduced by KIR, resulting in increased the ratio oxidized GSH to total GSH, and oxidation of tissue and bile. CSE and cystathione ß-synthase (CBS) expression were lowered in the liver after KIR. NAC administration increased total GSH and H2S levels in the liver and attenuated KIR-induced liver injuries. In contrast, Cse deletion caused the reduction of total GSH levels and worsened KIR-induced liver injuries, including primary cilia damage and abnormal bile secretion.

CONCLUSIONS:

These results indicate that KIR causes cholangiocyte damage, cholangiocytes primary cilia disruption, and abnormal bile secretion through reduced antioxidative ability of the liver.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bilis / Daño por Reperfusión / Cilios Límite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bilis / Daño por Reperfusión / Cilios Límite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos