Daradics 2022 PLoS One

From Bioblast
Publications in the MiPMap
Daradics N, Horvath G, Tretter L, Paal A, Fulop A, Budai A, Szijarto A (2022) The effect of Cyclophilin D depletion on liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy. https://doi.org/10.1371/journal.pone.0271606

Β» PLoS One 17:e0271606. PMID: 35834573 Open Access

Daradics Noemi, Horvath Gergo, Tretter Laszlo, Paal Agnes, Fulop Andras, Budai Andras, Szijarto Attila (2022) PLoS One

Abstract: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a modification of two-stage hepatectomy profitable for patients with inoperable hepatic tumors by standard techniques. Unfortunately, initially poor postoperative outcome was associated with ALPPS, in which mitochondrial dysfunction played an essential role. Inhibition of cyclophilins has been already proposed to be efficient as a mitochondrial therapy in liver diseases. To investigate the effect of Cyclophilin D (CypD) depletion on mitochondrial function, biogenesis and liver regeneration following ALPPS a CypD knockout (KO) mice model was created.

Male wild type (WT) (n = 30) and CypD KO (n = 30) mice underwent ALPPS procedure. Animals were terminated pre-operatively and 24, 48, 72 or 168 h after the operation. Mitochondrial functional studies and proteomic analysis were performed. Regeneration rate and mitotic activity were assessed.

The CypD KO group displayed improved mitochondrial function, as both ATP production (P < 0.001) and oxygen consumption (P < 0.05) were increased compared to the WT group. The level of mitochondrial biogenesis coordinator peroxisome proliferator-activated receptor Ξ³ co-activator 1-Ξ± (PGC1-Ξ±) was also elevated in the CypD KO group (P < 0.001), which resulted in the induction of the mitochondrial oxidative phosphorylation system. Liver growth increased in the CypD KO group compared to the WT group (P < 0.001).

Our study demonstrates the beneficial effect of CypD depletion on the mitochondrial vulnerability following ALPPS. Based on our results we propose that CypD inhibition should be further investigated as a possible mitochondrial therapy following ALPPS.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: HU Budapest Tretter L

Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Other 

Organism: Mouse  Tissue;cell: Liver  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS  Pathway: N, S  HRR: Oxygraph-2k 


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