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KMID : 1377020210180030399
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Tissue Engineering and Regenerative Medicine
2021 Volume.18 No. 3 p.399 ~ p.410
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IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice
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Kim Dae-Hwan
Chun So-Young
Lee Eun-Hye
Kim Bo-Mi
Yoon Bo-Hyun
Gil Hae-Jung
Han Man-Hoon
Ha Yun-Sok
Lee Jun-Nyung
Kwon Tae-Gyun
Kim Bum-Soo
Jang Byung-Ik
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Abstract
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BACKGROUND: High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively.
METHODS: To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High?fat dieted C57BL/6 mice and (4) High?fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods.
RESULTS: At week 12, high?fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro?inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups.
CONCLUSION: IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.
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KEYWORD
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IL-10 deficiency, Renal failure, Obesity, High-fat diet
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