Elafibranor Inhibits Chronic Kidney Disease Progression in NASH Mice
Table 3
In vitro effects of elafibranor in HFD-sera- or NC-sera-pretreated cultured podocytes/HK-2 monolayer.
Cultured podocytes monolayer
NC-sera
HFD-sera
HFD-sera+elaf
HFD-sera+elaf+siSITR1
HFD-sera+rSITR1
HFD-sera+rSITR1+BAF
SIRT1activity in (fold/buffer group) cell lysates
5.5 ± 0.31
0.44 ± 0.01
3.3 ± 0.06
1.1 ± 0.02
3.1 ± 0.8
1.3 ± 0.04
8-isoproatne (pg/mL) level in cell supernatant
462 ± 14
900 ± 5
484 ± 18
844 ± 10
517 ± 21
770 ± 11
autophagy flux index in cell supernatant
5.3 ± 0.2
1.5 ± 0.08
4.5 ± 0.5
2.1 ± 0.3
4.2 ± 0.4
2.3 ± 0.04
caspase 3/7 activity in cell supernatant (RU)
3 ± 0.08
9 ± 0.18
4.4 ± 0.06
6.6 ± 0.4
5 ± 0.6
7.5 ± 0.4
Concentration of FITC-alb in cell lysates
99 ± 22
44 ± 2
77 ± 3
58 ± 2
71 ± 8
52 ± 5
Cultured HK-2 cells monolayer
NC-sera
HFD-sera
HFD-sera+elaf
HFD-sera+elaf+siSITR1
HFD-sera+rSITR1
HFD-sera+rSITR1+BAF
SIRT1activity in (fold/buffer group) cell lysates
5 ± 0.28
0.4 ± 0.02
3 ± 0.04
1 ± 0.04
2.8 ± 0.7
1.2 ± 0.03
8-isoproatne (pg/mL) level in cell supernatant
420 ± 19
820 ± 4.5
440 ± 22
650 ± 42
480 ± 25
700 ± 16
autophagy flux index in cell supernatant
4.8 ± 0.3
1.4 ± 0.07
4.1 ± 0.3
1.9 ± 0.2
3.8 ± 0.6
2.1 ± 0.05
caspase 3/7 activity in cell supernatant (RU)
2 ± 0.06
8 ± 0.13
4 ± 0.05
6 ± 0.34
4.8 ± 0.7
6.9 ± 0.7
Concentration of FITC-alb in cell lysates
82 ± 17
40 ± 3
70 ± 2
52 ± 3
65 ± 10
49 ± 8
Data were showed as mean ± SD; HFD-sera/HFD-sera+elaf/HFD-sera+elaf+siSIRT1/HFD-sera+rSIRT1, HFD-sera+rSIRT1+BAF: HFD-sera-pretreated cells coincubated with vehicle, elaf+siSIRT1, rSIRT1, rSIRT1+BAF in HFD-sera-pretreated group; SIRT1 activity of buffer-group was assigned as 1; RU: relative light unit; autophagy flux index was calculated by the formula [autophagy flux index=LC3-II (indicator of autophagosomes formation) expression levels with Bafilomycin A1 (100ng/mL)/LC3-II expression levels without Bafilomycin-A1]. LC3-II expression was normalized by its GADPH expression level. Concentration of FITC-alb (higher value indicated better endocytosis/reuptake of albumin by podocytes/HK-2) in cell lysates;p<0.05 vs. vehicle-group; p<0.05, 0.01 vs. elaf- or rSIRT1 group; p<0.05 vs. NC-sera group.
