This study investigated whether chemerin/chemokine-like receptor 1 (CMKLR1) pathway participate in cisplatin‐induced spiral ganglion neuron (SGN) damage. Middle cochlear turn was collected from C57BL/6 mice and the SGNs were cultured. Cisplatin, 2-(anaphthoyl) ethyltrimethylammonium iodide (α-NETA), or recombinant mouse chemerin was added into the medium for the treatment. Relative mRNA and protein expression was determined by RT-PCR, ELISA and Western blot, respectively. In cultured mouse cochlear SGNs, the treatment of cisplatin enhanced the secretion of chemerin and CMKLR1. Recombinant chemerin promoted but α-NETA inhibited chemerin/CMKLR1 pathway in cisplatin stimulated SGNs. Cisplatin-induced apoptosis and inflammation response in SGNs were enhanced by recombinant chemerin while inhibited by α-NETA. Recombinant chemerin promoted but α-NETA inhibited NF-κB signal in cisplatin stimulated SGNs. In conclusion, chemerin/CMKLR1 pathway regulated apoptosis and inflammation response in cisplatin-induced SGN injury through NF-κB signaling pathway.
Introduction: Diabetic nephropathy (DN) is a common complication in diabetic patients. Chemerin, a novel adipokine, has been associated with renal damage in DN. The chemerin chemokine-like receptor 1 (CMKLR1) has been reported to participate in DN. In this study, we aimed to investigate the effect of a CMKLR1 antagonist, 2-(anaphthoyl)ethyltrimethylammonium iodide (α-NETA), on DN. Methods: To induce diabetes, 8-week-old male C57BL/6J mice were given a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Diabetic mice were randomly assigned to receive daily doses of 0, 5, or 10 mg/kg α-NETA for 4 weeks. Results: α-NETA dose-dependently induced body weight and reduced fasting blood glucose levels in STZ-induced diabetic mice. Furthermore, α-NETA significantly reduced the expressions of renal injury markers, including serum creatinine, kidney weight/body weight, urine volume, total proteins, and albumin in the urine, and increased creatinine clearance. Periodic acid-Schiff staining also indicated that α-NETA could effectively ameliorate renal injuries in DN mice. In addition, α-NETA inhibited renal inflammation and the expressions of chemerin and CMKLR1 in mice with DN. Conclusion: In summary, our findings suggested that α-NETA has beneficial effects on the management of DN. Specifically, α-NETA effectively ameliorated renal damage and inflammation in a dose-dependent manner in mice with DN. Thus, targeting the chemerin and CMKLR1 axis with α-NETA may be a promising therapeutic strategy for the treatment of DN
Xin Ning,Doudou Guo,Qing Huang,Cencen Wang,Yating Li,Yanfen Zhou,Xin Li
In mammals, chemerin and its receptor CMKLR1 might be downstream effectors in response to long photoperiod in the ependymal cells lining the third ventricle in rats. Iodothyronine deiodinase 2 (DIO2) is a main product of the involvement of TSH in photoperiodic signaling. Thus, the potential interplay of TSH and Chemerin/CMKLR1 signaling might exist during photoperiodic changes. Our study aimed to investigate whether Chemerin/CMKLR1 signaling could stimulate DIO2 production and how TSH could affect Chemerin/CMKLR1 signaling in primary rat ependymal cells. Colocalization of Chemerin with its receptor, CMKLR1, was observed using immunohistochemistry assay. The expression of chemerin and CMKLR1 was identified using real-time PCR and western blot analysis respectively. DIO2 expression, which involves a dual signaling pathway (an increase in cAMP levels and phosphorylation of ERK1/2, was detected by western blot assay and enzyme-linked immunosorbent assay (ELISA). Our study showed the potential interaction between Chemerin and CMKLR1 in primary rat ependymal cells. TSH could upregulate the expression of chemerin and CMKLR1 in Chemerin-pretreated primary ependymal cells. In vitro treatment of primary ependymal cells with Chemerin (10 ng/mL) or TSH (60 mIU/mL) could induce an increase in cAMP levels, ERK1/2 phosphorylation and DIO2 expression. Furthermore, we found that TSH could promote the effect of Chemerin/CMKLR1 signaling on DIO2 production through an increase in cAMP level and the phosphorylation of ERK1/2. We concluded that Chemerin/CMKLR1 signaling could enhance DIO2 activity in primary rat ependymal cells in vitro, and this effect could be promoted by TSH through cAMP and phosphorylation of ERK1/2.
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