Calcium‐sensing receptor mediates interleukin‐1β‐induced collagen expression in mouse collecting duct cells

• Published in: Journal of cellular biochemistry 2019-05, Vol.120 (5), p.7353-7362
• Main Authors: Wu, Min, Wang, Si‐Si, Cao, Jing‐Yuan, Tang, Tao‐Tao, Gao, Min, Ma, Kun‐Ling, Liu, Bi‐Cheng
• Format: Article
• Language: English
• Subjects: Antagonists; Calcium; Calcium-sensing receptors; calcium‐sensing receptor (CaSR); Catenin; Collagen; Collagen (type I); Collecting duct; collecting duct (CD) cells; Cytokines; Dkk1 protein; Interleukins; interleukin‐1β; Nuclear transport; Pharmacology; Proteins; siRNA; Sodium; Time dependence; Translocation; β‐catenin
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28010

The mechanisms that underlie the profibrotic effect of interleukin (IL)‐1β are complicated and not fully understood. Recent evidence has suggested the involvement of the calcium‐sensing receptor (CaSR) in tubular injury. Therefore, the current study aimed to investigate whether CaSR mediates IL‐1β‐induced collagen expression in cultured mouse inner medullary collecting duct cells (mIMCD3) and to determine the possible downstream signaling effector. The results showed that IL‐1β significantly upregulated the expression of type I and III collagens in a concentration‐ and time‐dependent manner. Moreover, CaSR was expressed in mIMCD3 cells, and its expression was increased by increasing the concentrations and times of IL‐1β treatment. Selective inhibitors (Calhex231 or NPS2143) or the siRNA of CaSR attenuated the enhanced expression of type I and III collagens. Furthermore, IL‐1β increased nuclear β‐catenin protein levels and decreased cytoplasmic β‐catenin expression in cells. In contrast, blockage of CaSR by the pharmacological antagonists or siRNA could partially attenuate such changes in the IL‐1β‐induced nuclear translocation of β‐catenin. DKK1, an inhibitor of β‐catenin nuclear translocation, further inhibited the expression of type I and III collagens in cells treated with IL‐1β plus CaSR antagonist. In summary, these data demonstrated that IL‐1β‐induced collagen I and III expressions in collecting duct cells might be partially mediated by CaSR and the downstream nuclear translocation of β‐catenin. The effect of IL‐1β on the expression of extracellular matrix proteins in renal collecting duct cells and its underlying mechanisms remain largely unknown. The current study demonstrated that IL‐1β‐induced collagen I and III expression in mIMCD3 cells might be partially mediated by calcium‐sensing receptor and the downstream nuclear translocation of β‐catenin.