Tissue Eng Regen Med.  2021 Jun;18(3):399-410. 10.1007/s13770-020-00328-7.

IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice

Affiliations
  • 1Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, Daegu 42415, Republic of Korea
  • 2BioMedical Research Institute, Kyungpook National University Hospital, Daegu 41944, Republic of Korea
  • 3Department of Pathology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
  • 4Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, Korea
  • 5Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
  • 6Department of Internal Medicine, School of Medicine, Yeungnam University, Daegu, Republic of Korea

Abstract

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.

Keyword

IL-10 deficiency; Renal failure; Obesity; High-fat diet
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