Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin

Abstract

Chronic kidney disease is a major global public health problem. The peptide hormones adropin and spexin modulate many physiological functions such as energy balance and glucose, lipid and protein metabolism. However, it is unclear whether these peptides may exert effects on renal damage, tissue remodeling, and inflammatory conditions. In view of the limited information, we aimed to investigate the effect of adropin and spexin on matrix metalloproteinase and inflammatory response genes a rat model of adenine-induced chronic kidney failure. Chronic kidney failure was induced in rats by administering adenine hemisulfate. Renal function was determined in an autoanalyzer. Histopathological modifications were assessed by H&E staining. mRNA expression levels of ALOX 15, COX 1, COX 2, IL-1β, IL-10, IL-17A, IL-18 IL-21, IL-33, KIM-1, MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, NGAL, TGFβ1, TIMP-1, and TNFα in kidney tissue were measured by qPCR. Our results showed an increase of 24-h urine volume, serum creatinine, BUN, and urine protein levels in group with adenine-induced CKF. Adropin and spexin treatments decreased urine protein and 24-h urine volume. Renal damage, TIMP-1, IL-33, and MMP-2 increased after CKF induction, while COX 1, MMP-9, and MMP-13 levels were significantly reduced. Furthermore, KIM-1, TIMP-1, IL-33, and MMP-2 were downregulated by spexin treatment. Renal damage, NGAL, TIMP-1 IL-17A, IL-33, MMP-2, and MMP-3 decreased after adropin treatment, while MMP-13 levels were upregulated. Treatment with adropin+spexin decreased KIM-1, NGAL, TIMP-1, IL-1β, IL-17A, IL-18, IL-33, ALOX 15, COX 1, COX 2, TGFβ1, TNFα, MMP-2, MMP-3, and MMP-7, but increased MMP-13 levels. Our findings revealed that inflammatory response and MMP genes were modulated by adropin and spexin. These peptides may have protective effects on inflammation and chronic kidney damage progression.

Determination of adropin, body mass index and other biochemical parameters in Iraqi type II diabetic patients

“…The finding of the current study agreed with results previously reported by (43) that found serum Adropin levels were inversely correlated with adverse metabolic parameters including FBS, HbA1C, HOMA-IR and fasting insulin and agreed with (44), as well as (45)showed opposite to current study which reported Serum adropin has negative correlation with HbA1C and fasting insulin and BMI , one possible reason that adropin plays an important role in maintaining metabolic homeostasis, increasing glucose utilization at the expense of fatty acids, improving glucose tolerance, and reducing insulin resistance. The differences between the studies it was highly probable that our observations in T2DM were confounded by variations in disease duration, diabetic complications Metabolically, adropin regulates the activities of the principal pancreatic hormones that control the fate of glucose and fatty acids.…”

Impact of spexin on metabolic diseases and inflammation: An updated minireview

“…Also, SPX treatment reduced metalloproteinase-2 (MMP2) levels, which regulates the fibrotic process. 56 These results indicate the protective effect of SPX on renal damage.…”

“…19 Furthermore, SPX treatment decreased IL-33 gene expression in kidney tissue in adenine-induced CRF in rats. 56 In the same experiment, SPX treatment reduced serum IL-5, granulocyte colony-stimulating factor (G-CSF), and IFN-γ levels. 70 Unlike animal studies, there was no observed correlation between SPX and hs-CRP in PCOS patients compared with the control group.…”

Effect of Fushengong Decoction on PTEN/PI3K/AKT/NF-κB Pathway in Rats With Chronic Renal Failure via Dual-Dimension Network Pharmacology Strategy

“…Studies have shown that AKT is the key node of PTEN/PI3K/AKT/NF-κB signaling pathway ( Xu J et al, 2021 ; Xu K. et al, 2021 ). In addition, inflammatory response, hormones, and apoptosis are involved in the process of CRF ( Li H et al, 2021 ) ( Wang et al, 2019 ; Yazgan et al, 2021 ). HIF-1 signaling pathway, ErbB signaling pathway, estrogen signaling pathway and other pathways need to be further studied to find new targets for the treatment of CRF.…”