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. 2018 Sep 27:24:6832-6839.
doi: 10.12659/MSM.909810.

CD36 Promotes Podocyte Apoptosis by Activating the Pyrin Domain-Containing-3 (NLRP3) Inflammasome in Primary Nephrotic Syndrome

Xuejun Yang  1 , You Wu  1 , Qianqian Li  1 , Gaofu Zhang  2 , Mo Wang  2 , Haiping Yang  2 , Qiu Li  2
Affiliations

CD36 Promotes Podocyte Apoptosis by Activating the Pyrin Domain-Containing-3 (NLRP3) Inflammasome in Primary Nephrotic Syndrome

Xuejun Yang et al. Med Sci Monit. .

Abstract

BACKGROUND CD36 plays a critical role in many sterile inflammatory diseases, including type 2 diabetes mellitus, atherosclerosis, and primary nephrotic syndrome. This study investigated whether CD36 activates the nucleotide-binding domain leucine-rich repeat-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and promotes podocytes apoptosis in primary nephrotic syndrome. MATERIAL AND METHODS The mouse podocyte cell line MPC5 was used as a model. mRNA and protein expression of CD36 and NLRP3 was quantified by real-time PCR and Western blotting, respectively. Levels of caspase-1 activity and total cholesterol were determined using commercial kits. Intracellular lipid droplets were detected by Oil Red O staining. CD36 expression was also examined in nephrotic mouse kidney tissue by immunohistochemistry and immunofluorescence. Intracellular lipid droplet was examined by Oil Red O staining. RESULTS CD36 expression was increased in nephrotic mouse kidney tissue. Treatment with interleukin-1b increased expression of CD36 and total cholesterol in MPC5 cells. Moreover, this treatment increased expression of NLRP3 and the percentage of apoptotic cells, both of which were inhibited by co-treatment with an anti-CD36 antibody. CONCLUSIONS CD36 might play an important role in podocyte apoptosis by activating the NLRP3 inflammasome in primary nephrotic syndrome.

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Conflict of interest statement

Conflict of interests

None.

Figures

Figure 1
Figure 1
CD36 expression is increased in nephrotic mouse kidney tissue. CD36 expression in kidney tissue of mice from the ADR and CTR groups was investigated by immunohistochemistry (A) and immunofluorescence (B). Scale bars: A, 50 μm; B, 100 μm.
Figure 2
Figure 2
Treatment with LDL and IL-1β increases CD36 expression in MPC5 cells. mRNA and protein expression of CD36 in MPC5 cells treated as indicated was investigated by quantitative RT-PCR (A) and Western blotting (B), respectively. *, *** p<0.05 vs. CTR cells; **, **** p<0.05 vs. LDL+IL-1β-treated cells.
Figure 3
Figure 3
Treatment with LDL and IL-1β induces apoptosis of MPC5 cells via CD36. MPC5 cells were treated as indicated for 48 h and the percentage of apoptotic cells was determined by flow cytometry. (A) Flow cytometric plots. (B) Percentage of apoptotic cells. * p<0.05 vs. CTR cells; ** p<0.05 vs. CTR cells; *** p<0.05 vs. LDL+IL-1β-treated cells.
Figure 4
Figure 4
Treatment with LDL and IL-1β promotes lipid accumulation in MPC5 cells via CD36. MPC5 cells were treated as indicated. Lipid accumulation was investigated by Oil Red O staining (A) and the total cholesterol level was determined using a commercial kit (B). *, ** p<0.05 vs. CTR cells; *** p<0.05 vs. LDL+IL-1β-treated cells. Scale bars: 50 μm.
Figure 5
Figure 5
Treatment with LDL and IL-1β activates the NLRP3 inflammasome in MPC5 cells via CD36. MPC5 cells were treated as indicated. Protein expression of NLRP3 (A) and caspase-1 activity (B) were determined by Western blotting and using a commercial kit, respectively. *, *** p<0.05 vs. CTR cells; **, **** p<0.05 vs. LDL+IL-1β-treated cells.
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