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Aims: The study aimed to investigate the renoprotective effect of glucagon-like peptide-1 (GLP-1) against renal tubular injury in C57BL/6 mice induced by a high-fat diet (HFD). Methods: Twenty C57BL/6 mice were fed HFD for 12 weeks. Ten of these mice were treated with GLP-1 at 200 μg/kg subcutaneously twice daily for 4 weeks (HFDG group), and the other ten mice received vehicle only (HFD group). Ten mice fed standard rodent chow served as controls (Con group). Body weight, kidney weight, food intake, and systolic blood pressure were measured. The expression of endoplasmic reticulum stress (ERS) markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis in the kidney were examined utilizing western blotting, immunohistochemistry and TUNEL, respectively. Angiotensin II and angiotensin II type 1 receptor (AT1R) were examined by ELISA. Human proximal tubule epithelial cells (HK2) were treated with GLP-1(150 nM) followed by treatment with palmitic acid (500 nM [PA]) for 24 h. HK2 cells treated with BSA were used as controls. The protein levels of ERS markers, apoptosis-associated protein, and AT1R were measured by western blotting. Results: Increase of body weight, food intake, and systolic blood pressure was less pronounced in GLP-1 treated HFDG mice compared to HFD mice. The levels of ERS markers (BIP, p-eIF2α, ATF4, and CHOP) and apoptosis decreased following GLP-1 treatment in vivo and in vitro (p<0.05). Increased AT1R induced by HFD and PA were blocked with GLP-1 treatment. In contrast, the level of angiotensin II after GLP-1 treatment was not significantly different between the HFD and HFDG mice. Conclusion: The study indicated that saturated fatty acids induced ERS and apoptosis in the kidney and increased AT1R expression. GLP-1 treatment exerted renoprotective effects against saturated fatty acid-induced kidney tubular cell ERS and apoptosis together with inhibition of AT1R expression in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Objective: To identify novel potential biomarkers and evaluate combined biomarkers for diagnosing kidney injury with considerable accuracy in preeclampsia. Methods: The level of serum and urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), retinol-binding protein (RBP) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. Results: The level of serum cystatin C, urine RBP, urine NGAL and urine KIM-1 in preeclampsia group were higher than that in the normal pregnancy group. When four biomarkers are combined, the sensitivity and specificity are 100%/98.20%. Conclusion: Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. The more biomarkers combined, the more sensitivity and specificity were increased. [ABSTRACT FROM AUTHOR]

Previously we identified four Tocilizumab mimotopes and antibodies induced by these mimotopes could bind to IL-6R (interleukin-6 receptor) and regulate the downstream signaling pathways. On the basis of obtained research data, we sought to investigate whether the therapeutic strategies by Tocilizumab mimotope vaccination could be effective in the renal fibrosis model and show the desired activity by inhibiting IL-6 signaling in current study. We immunized the mice with the Tocilizumab mimotope and then performed the unilateral ureteric obstruction (UUO) surgery. Masson-trichrome staining and immunohistochemistry were performed to evaluate the renal fibrosis. The activations and differentiations of F4/80+ cells in the spleens and kidneys were detected by flow cytometry, immunohistochemistry and immunofluorescence. Signaling pathways involved IL-6, pro-fibrotic and ferroptosis were analyzed by immunoblot assay. The free iron and lipid oxidation end product were performed by Prussian blue staining and immunohistochemistry. The injury and apoptosis in the kidneys were evaluated by immunofluorescence. The results showed the mimotope vaccination could reduce the level of fibrosis, injury and apoptosis by down-regulating the pro-fibrotic proteins, alleviating the activations and differentiations of macrophage F4/80+ cells in UUO models. IL-6/ERK signaling pathway was inhibited with the mimotope vaccination. The ferroptosis inhibited proteins significantly increased after the mimotope vaccination. On the contrary, the levels of free iron and lipid oxidation end product were observed to decrease in the mimotope treatment group. Our results suggested that the Tocilizumab mimotope vaccination might be an alternative therapy to against renal fibrosis. • The Tocilizumab mimotope can ameliorate renal fibrosis in the animal model. • The levels of fibrotic proteins decreased with the mimotope immunization. • The mimotope can reduce the macrophages in the kidney and spleen. • The mimotope can inhibit ERK but not STAT3 signaling. • The mimotope can inhibit ferroptosis in the kidney tissue. [ABSTRACT FROM AUTHOR]