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![Impaired autophagy and upregulated
glycolysis levels in IECs were observed under inflammatory
conditions. (A) Establishment of acute colitis mouse model and
chronic colitis mouse model. (B) The protein levels of P62 and LC3b
in colonic epithelial cells of acute DSS-induced mice (n=3) and
chronic DSS-induced mice (n=3) determined by western blot analysis.
(C) mRNA levels of PFKP, LDHA, HK2, PKM2, PFKFB3 in DSS-induced
mice epithelial cells. (D) Autophagic flux was measured by
transfecting cells with mRFP-GFP-LC3 dual-fluorescence adenovirus
(Ad-LC3), allowing differentiation between autophagosomes
(mRFP+/GFP+ fluorescence, appearing as yellow puncta) and
autolysosomes (mRFP+/GFP-fluorescence, appearing as red puncta).
TNF-α (200 ng/ml) induced epithelial cells for 48 h. Representative
immunofluorescence images were shown. (Original magnification,
×20). Quantification of LC3 puncta number of representative cells.
(E) Relative glucose content and lactate (Lac) production in
control vs. TNF-α induced epithelial cells. (F) 2-NBDG and (G)
BCECF fluorescent counter-staining in TNF-α induced epithelial
cells vs. control. Representative immunofluorescence images were
shown. (Original magnification, ×20). Quantitative fluorescence
intensity of 2-NBDG and BCECF (n=3). Data were presented as the
mean ± SD of n=3 per group. Statistical analysis was performed
using unpaired t-tests. ****P<0.0001,
***P<0.001, **P<0.01,
*P<0.05, ns, non-significant vs. control group. IECs,
intestinal epithelial cells; DSS, dextran sulfate sodium salt;
2-NBDG, 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)
amino]-D-glucose; BCECF, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein.](/article_images/ijmm/57/2/ijmm-57-02-05714-g00.jpg)
![Knockdown of ATG7 in IECs resulted in
increased glycolysis levels. (A) mRNA levels of ATG7 in control vs.
sh-ATG7 epithelial cells. (B) Relative glucose content and lactate
(Lac) production in control vs. sh-ATG7 epithelial cells. (C)
2-NBDG and (D) BCECF fluorescent counter-staining in ATG7 knockdown
epithelial cells vs. control. Representative immunofluorescence
images were shown. (Original magnification, ×20). Quantitative
fluorescence intensity of 2-NBDG and BCECF. (E) Enzymatic
activities of PFK-1 in ATG7-knockdown epithelial cells vs. control
(n=3). P-values were calculated using an unpaired t-test. The
values were presented as the means ± SEM, n=3,
*P<0.05, **P<0.01,
***P<0.001, ****P<0.0001. ATG,
autophagy related gene; IECs, intestinal epithelial cells; sh,
short hairpin; si, small interfering; 2-NBDG,
2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose;
BCECF, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; PFK-1,
phosphofructokinase-1.](/article_images/ijmm/57/2/ijmm-57-02-05714-g01.jpg)
![Autophagy agonists and inhibitors
regulated glycolysis. (A) Relative glucose content and Lac
production in control vs. Baf A1 treated IECs. (B) Relative glucose
content and Lac production in control vs. rapamycin treated IECs.
(C and D) 2-NBDG and BCECF fluorescent counter-staining in
rapamycin or BafA1 treated IECs vs. control. Representative
immunofluorescence images were shown. (Original magnification,
×20). Quantitative fluorescence intensity of 2-NBDG and BCECF
(n=3). (E) Enzymatic activities of PFK-1 in rapamycin or BafA1
treated IECs vs. control (n=3). P-values were calculated using
One-way ANOVA followed by Tukey's post-hoc test. The values were
presented as the means ± SEM, *P<0.05,
**P<0.01, ***P<0.001,
****P<0.0001. Lac, lactate; Baf A1, bafilomycin A1;
IECs, intestinal epithelial cells; 2-NBDG,
2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose;
BCECF, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; PFK-1,
phosphofructokinase-1.](/article_images/ijmm/57/2/ijmm-57-02-05714-g02.jpg)
![PFKFB3 played a key role in autophagy
regulating of the glycolysis of IECs. (A) The verification of
PFKFB3 knockdown and overexpression by western blotting. Relative
glucose content and Lac production in PFKFB3 knockdown IECs treated
with (B) Baf A1 (200 nM) or (E) rapamycin (200 nM). (C and F)
2-NBDG and (D and G) BCECF fluorescent counter-staining in
rapamycin or BafA1 treated PFKFB3 knockdown IECs vs. control.
Representative immunofluorescence images are shown. (Original
magnification, ×20) with quantitative fluorescence intensity of
2-NBDG and BCECF (n=3). (H) Relative glucose content and Lac
production in PFKFB3 OE IECs treated with rapamycin (200 nM). (I)
2-NBDG and (J) BCECF fluorescent counter-staining in rapamycin
treated PFKFB3 OE IECs vs. control. Representative
immunofluorescence images are shown (Original magnification, ×20)
and quantitative fluorescence intensity of 2-NBDG and BCECF (n=3).
P-values were calculated using One-way ANOVA followed by Tukey's
post-hoc test. The values were presented as the means ± SEM,
*P<0.05, **P<0.01,
***P<0.001, ****P<0.0001. PFKFB3,
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3; Lac,
lactate; IECs, intestinal epithelial cells; Baf A1, bafilomycin A1;
2-NBDG, 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)
amino]-D-glucose; BCECF, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; OE,
overexpression.](/article_images/ijmm/57/2/ijmm-57-02-05714-g04.jpg)
