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CCR2 knockout ameliorates obesity-induced kidney injury through inhibiting oxidative stress and ER stress


Autoři: Seung Joo Lee aff001;  Jeong Suk Kang aff001;  Hong Min Kim aff003;  Eun Soo Lee aff003;  Ji-Hye Lee aff004;  Choon Hee Chung aff003;  Eun Young Lee aff001
Působiště autorů: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea aff001;  Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University, Cheonan, Korea aff002;  Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea aff003;  Department of Pathology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222352

Souhrn

CCL2/CCR2 signaling is believed to play an important role in kidney diseases. Several studies have demonstrated that blocking of CCR2 has a therapeutic effect on kidney diseases. However, the effects of CCR2 knockout on obesity-induced kidney injury remain unclear. We investigated the therapeutic effects and the mechanism of CCL2/CCR2 signaling in obesity-induced kidney injury. We used C57BL/6-CCR2 wild type and C57BL/6-CCR2 knockout mice: Regular diet wild type (RD WT), RD CCR2 knockout (RD KO), High-fat diet WT (HFD WT), HFD CCR2 KO (HFD KO). Body weight of WT mice was significantly increased after HFD. However, the body weight of HFD KO mice was not decreased compared to HFD WT mice. Food intake and calorie showed no significant differences between HFD WT and HFD KO mice. Glucose, insulin, total cholesterol, and triglycerides levels increased in HFD WT mice were decreased in HFD KO mice. Insulin resistance, increased insulin secretion, and lipid accumulation showed in HFD WT mice were improved in HFD KO mice. Increased desmin expression, macrophage infiltration, and TNF-α in HFD mice were reduced in HFD KO mice. HFD-induced albuminuria, glomerular hypertrophy, glomerular basement membrane thickening, and podocyte effacement were restored by CCR2 depletion. HFD-induced elevated expressions of xBP1, Bip, and Nox4 at RNA and protein levels were significantly decreased in HFD KO. Therefore, blockade of CCL2/CCR2 signaling by CCR2 depletion might ameliorate obesity-induced albuminuria through blocking oxidative stress, ER stress, and lipid accumulation.

Klíčová slova:

Biology and life sciences – Ecology – Community ecology – Trophic interactions – Anatomy – Renal system – Kidneys – Physiology – Physiological parameters – Obesity – Biochemistry – Hormones – Cell biology – Cellular types – Animal cells – Blood cells – White blood cells – Macrophages – Immune cells – Ecology and environmental sciences – Medicine and health sciences – Body weight – Endocrinology – Diabetic endocrinology – Insulin – Endocrine physiology – Immunology – Research and analysis methods – Animal studies – Experimental organism systems – Model organisms – Mouse models – Animal models


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