KIR6.2 protein defficency affects normal liver regeneration after partial hepatectomy in mice

LORENZETTI, F; VERA, MC; HEIT-BARBINI, FJ; HESSE, L; COMANZO, CG; LUCCI, A; PISANI, GB; CEBALLOS, MP; QUIROGA, AD; ALVAREZ, ML

Congreso; SAFIS; 2019

Liver regeneration (LR) after two-thirds partial hepatectomy (PH) in rodents has become a useful paradigm for studying the unique capacity of the organ to regenerate. Many signals come into play to drive normal LR, among them hepatic ATP content needs to be conserved. Kir6.2/K-ATP channels are expressed in the liver and they play critical roles in the cellular responses for tissue protection under stress. Previous results from our group showed that Kir6.2 knockout mice (Kir6.2-/-) displayed a significant diminution in hepatic PCNA and cyclin D1 protein levels at 48 h post-PH, indicating a possible participation of Kir6.2 in LR. Aim: to evaluate the role of Kir6.2 in LR after PH. Methods and Results: Male C57/B6 wild type (WT) and Kir6.2-/- mice were subjected to PH. LR was evaluated at the different phases of LR: priming (1, 2 and 3h), proliferation (48 and 96h) and termination (168 h) phases after PH. Liver to body weight ratio (LW/BW) showed a reduction in Kir6.2-/- mice at the studied times (1h post-PH: WT= 2.04±0.15; Kir6.2-/-= 1.61±0.10*; 2h post-PH: WT= 2.16±0.15; Kir6.2-/-= 1.70±0.07*; 3h post-PH: WT= 2.11±0.15; Kir6.2-/-= 1.58±0.10*; 48h post-PH: WT= 3.10±0.02; Kir6.2-/-= 2.55±0.19*; 96h post-PH: WT= 3.58±0.26; Kir6.2-/-= 2.62±0.29*; 168h post-PH: WT= 4.82±0.19; Kir6.2-/-= 3.89±0.09*; data are expressed as percent values and are means ± SEM; n=5; *p