Journal: Frontiers in Cell and Developmental Biology

Article Title: Multi-omics integration identifies Acsm2/ACSM2A deficiency as a metabolic driver of ZBP1-mediated PANoptosis in acute kidney injury

doi: 10.3389/fcell.2026.1936504

Figure Lengend Snippet: Acsm2/ACSM2A is downregulated in renal tubular epithelial cells from three distinct AKI mouse models and in OGD/R-induced cell models. (A) A schematic diagram showing the construction of the IRI-induced AKI mouse model. (B,C) Renal function was assessed by measuring serum creatinine (B) and BUN (C) in a mouse model of IRI-induced AKI (mice n = 5). (D) Transcriptional level of Acsm2 in IRI-induced AKI mouse model (mice n = 5). (E) Western blot analysis of Acsm2 protein expression in a mouse model of IRI-induced AKI. (F) A schematic diagram showing the construction of the FA-induced AKI mouse model. (G,H) Renal function was assessed by measuring serum creatinine (G) and BUN (H) in a mouse model of FA-induced AKI (mice n = 5). (I) Transcriptional level of Acsm2 in FA-induced AKI mouse model (mice n = 5). (J) Western blot analysis of Acsm2 protein expression in a mouse model of FA-induced AKI. (K) A schematic diagram showing the construction of the Cisplatin-induced AKI mouse model. (L,M) Renal function was assessed by measuring serum creatinine (L) and BUN (M) in a mouse model of Cisplatin-induced AKI (mice n = 5). (N) Transcriptional level of Acsm2 in Cisplatin-induced AKI mouse model (mice n = 5). (O) Western blot analysis of Acsm2 protein expression in a mouse model of Cisplatin-induced AKI. (P) Transcriptional level of ACSM2A in OGD/R-induced HK-2 cell models ( n = 3). (Q) Western blot analysis of ACSM2A protein expression in OGD/R-induced HK-2 cell models. (R) Transcriptional level of ACSM2A in OGD/R-induced primary human TECs models ( n = 3). Data are representative of three independent experiments (E, J, O, Q). Error bars are shown as mean ± SD with n = 3 (P, R) or n = 5 (B-D, G-I, L-N) biological replicates. Two-tailed unpaired Student’s t-test (B-D, G-I, L-N, P, R). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, NS, not significant.

Article Snippet: To establish the folic acid (FA)- or cisplatin-induced acute kidney injury (AKI) model, mice received a single intraperitoneal injection of FA (200 mg/kg; MCE, HY-16637) or cisplatin (10 mg/kg; MCE, HY-17394).

Techniques: Western Blot, Analysis, Expressing, Two Tailed Test

Journal: Frontiers in Cell and Developmental Biology

Article Title: Multi-omics integration identifies Acsm2/ACSM2A deficiency as a metabolic driver of ZBP1-mediated PANoptosis in acute kidney injury

doi: 10.3389/fcell.2026.1936504

Figure Lengend Snippet: ACSM2A downregulation promotes PANoptosis in renal tubular epithelial cells during AKI. (A) LDH release from control and OGD/R-treated HK-2 cells as a measure of cytotoxicity ( n = 6). (B) Cell death quantification in control and OGD/R-treated HK-2 cells ( n = 6). (C) Western blot analysis of Caspase 3, Cleaved-caspase 3 (c-caspase3), MLKL, Phosphorylated-MLKL (p-MLKL), GSDMD and Cleaved-GSDMD (c-GSDMD) protein expression in control and OGD/R-treated HK-2 cells. (D) Cell death quantification in control and OGD/R-treated HK-2 cells, pre-treated with dimethylsulfoxide (DMSO; control), 20 µM Z-VAD-FMK, 10 µM Disulfiram, 10 µM GSK-872 or a combination of all three inhibitors for 1 h ( n = 3). (E) Cytotoxicity assessed by LDH release from HK-2 cells following siRNA-mediated knockdown of ACSM2A for 48 h ( n = 3). (F) Cell death quantification in HK-2 cells following siRNA-mediated knockdown of ACSM2A for 48 h ( n = 3). (G) Cell death quantification in HK-2 cells transfected with ACSM2A siRNA for 24 h, followed by treatment with DMSO (control), 20 µM Z-VAD-FMK, 10 µM disulfiram, 10 µM GSK-872, or a combination of all three inhibitors for an additional 24 h ( n = 3). (H) Cell death quantification in HK-2 cells transfected with ACSM2A siRNA for 48 h and subsequently subjected to control or OGD/R treatment ( n = 3). (I) Cell death quantification in HK-2 cells overexpressing of ACSM2A for 48 h and subsequently subjected to control or OGD/R treatment ( n = 3). (J) Western blot analysis of ACSM2A and GAPDH were conducted in control HK-2 cells, cells subjected to ACSM2A knockdown, and cells in which ACSM2A was overexpressed subsequent to ACSM2A knockdown. (K) Cell death quantification in HK-2 cells under the indicated treatment conditions, as shown in Fig. (J) ( n = 3). (L) Western blot analysis of Caspase 3, Cleaved-caspase 3 (c-caspase3), MLKL, Phosphorylated-MLKL (p-MLKL), GSDMD and Cleaved-GSDMD (c-GSDMD) protein expression in HK-2 cells under the indicated treatment conditions, as shown in Fig. (J) . (M) Cell death quantification in primary human TECs under the indicated treatment conditions, as shown in Fig. J ( n = 3). Data are representative of three independent experiments (C, J, L) . Error bars are shown as mean ± SD with n = 3 (D-I, K, M) or n = 6 (A,B) biological replicates. Two-tailed unpaired Student’s t-test (A,B,E,F) . One-way ANOVA with Tukey’s multiple comparisons test (D, G, H, I, K, M) . * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, NS, not significant.

Article Snippet: To establish the folic acid (FA)- or cisplatin-induced acute kidney injury (AKI) model, mice received a single intraperitoneal injection of FA (200 mg/kg; MCE, HY-16637) or cisplatin (10 mg/kg; MCE, HY-17394).

Techniques: Control, Western Blot, Analysis, Expressing, Knockdown, Transfection, Two Tailed Test

Journal: Frontiers in Cell and Developmental Biology

Article Title: Multi-omics integration identifies Acsm2/ACSM2A deficiency as a metabolic driver of ZBP1-mediated PANoptosis in acute kidney injury

doi: 10.3389/fcell.2026.1936504

Figure Lengend Snippet: ACSM2A deficiency in renal tubular epithelial cells promotes ZBP1-mediated PANoptosis by inducing mitochondrial oxidative stress and Z-nucleic acid accumulation. (A) Intracellular ATP levels in control HK-2 cells, ACSM2A-knockdown cells, and ACSM2A-knockdown cells with ACSM2A overexpression. (B,C) Representative fluorescence images (B) and quantitative analysis (C) of MitoSox in control HK-2 cells, ACSM2A-knockdown cells, and ACSM2A-knockdown cells with ACSM2A overexpression. Red fluorescence indicates MitoSox (mitochondrial superoxide). (D,E) Representative fluorescence images (D) and quantitative analysis (E) of DCFH-DA in control HK-2 cells, ACSM2A-knockdown cells, and ACSM2A-knockdown cells with ACSM2A overexpression. Green fluorescence indicates DCFH-DA (ROS). (F,G) Representative fluorescence images (F) and quantification (G) of Z22 levels in control HK-2 cells, ACSM2A-knockdown cells, ACSM2A-knockdown cells with ACSM2A overexpression, ACSM2A-knockdown cells treated with mito-TEMPO (10 μM) for 24 h and control HK-2 cells treated with MitoPQ (10 μM) for 12 h. Green fluorescence indicates Z22 (Z-NA). Blue fluorescence indicates DAPI (nucleus). (H) Cell death quantification in control HK-2 cells, ACSM2A-knockdown cells, and ACSM2A-knockdown cells treated with mito-TEMPO (10 μM) for 24 h ( n = 3). (I) Cell death quantification in control HK-2 cells, ACSM2A-knockdown cells, and ACSM2A-knockdown cells with ZBP1 knockdown ( n = 3). Data are representative of three independent experiments (B,D,F) . Error bars are shown as mean ± SD with n = 3 (A,C,E,H,I) or n = 6 (G) biological replicates. One-way ANOVA with Tukey’s multiple comparisons test (A,C,E,G,H,I) . * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, NS, not significant.

Article Snippet: To establish the folic acid (FA)- or cisplatin-induced acute kidney injury (AKI) model, mice received a single intraperitoneal injection of FA (200 mg/kg; MCE, HY-16637) or cisplatin (10 mg/kg; MCE, HY-17394).

Techniques: Control, Knockdown, Over Expression, Fluorescence, Analysis