Zinc Deficiency Aggravation of ROS and Inflammatory Injury Leading to Renal Fibrosis in Mice

• Published in: Biological trace element research 2021-02, Vol.199 (2), p.622-632
• Main Authors: Xu, Ran, Chen, Miao-yu, Liang, Wan, Chen, Yu, Guo, Meng-yao
• Format: Article
• Language: English
• Subjects: Actin; Animal models; Antioxidants; Biochemistry; Biomedical and Life Sciences; Biotechnology; Collagen; Collagen (type I); Creatinine; DNA; ELISA; Enzyme-linked immunosorbent assay; Extracellular; Extracellular matrix; Fibronectin; Fibrosis; Gelatinase A; Gelatinase B; Hyperemia; Inflammation; Interstitial collagenase; Kidneys; Life Sciences; Matrilysin; Matrix metalloproteinase; Matrix metalloproteinases; Muscles; Necrosis; Nucleotide sequence; Nutrient deficiency; Nutrition; Oncology; Oxidative stress; PCR; Polymerase chain reaction; Regulators; Smooth muscle; Tissue; Tissue inhibitor of metalloproteinase 1; Trace elements; Transforming growth factor-b1; Tumor necrosis factor-α; Urea; Vasodilation; Zinc
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-020-02184-x

Zinc (Zn) is a trace element with a variety of anti-inflammatory and antioxidant effects. Zn deficiency is related to tissue fibrosis. The present study was designed to investigate the effect of Zn on renal fibrosis. Mouse models were successfully established by feeding mice diets with different concentrations of Zn. Zn deficiency induced a decrease in Zn levels in kidney tissue. The results also revealed renal vasodilation, hyperemia, and inflammatory cell infiltration, and the levels of creatinine and urea nitrogen were increased. Furthermore, the TUNEL results showed a large degree of renal cell necrosis caused by Zn deficiency. Meanwhile, the corresponding antioxidant and anti-inflammatory regulators (MT-1, MT-2, Nrf2, and TGF-β1) were detected by RT-PCR, showing that the expression of MT-1, MT-2, and Nrf2 decreased but that TGF-β1 expression increased. The results of Sirius red staining proved that the expression of collagen was increased by Zn deficiency. The immunohistochemical experiments found that the expression of α-smooth muscle actin (α-SMA) increased. ELISA showed that the expression of Collagen I, III, and IV; fibronectin (FN); and inflammatory factors (TNF-α and IL-1β) were remarkably increased. The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, and TIMP-1, which are extracellular matrix-regulating molecules, was detected by RT-PCR. The results showed that the expression of TIMPs was increased but that the expression of MMPs was decreased. We also obtained consistent results in vivo. All the experimental results indicated that Zn deficiency could aggravate fibrosis by increasing inflammation in the kidney.