title: Low Dose Cadmium Inhibits Proliferation of Human Renal Mesangial Cells via Activation of the JNK Pathway.
abstract: Cadmium (Cd) is a heavy metal and environmental pollutant. The kidney is the principal target organ of Cd exposure. Previously, we found that low concentration of Cd damages the integrity of the glomerular filtration barrier. However, little is known about the effects of Cd on renal mesangial cells, which provide structural support for the glomerular capillary loops and regulate intraglomerular blood flow. In this study, human renal mesangial cells (HRMCs) were cultured in the presence of serum and treated with 4 μM Cd. We found that Cd activates the c-Jun N-terminal kinase (JNK) pathway, and increases the protein levels of c-Jun and c-Fos. Cd treatment also induces a decrease in proliferation and an increase in apoptosis of HRMCs, but only the decrease in HRMC proliferation was reversed by pretreatment with SP600125, an inhibitor of the JNK pathway. In addition, Cd does not change the expression of α-smooth muscle actin and platelet-derived growth factor receptor-β, the markers of mesangial cells, or the alignment of the filamentous actin (F-actin) cytoskeleton of HRMCs. Our data indicate that the JNK pathway mediates the inhibitory effects of Cd on HRMC proliferation.
authors.affiliation: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China. chenxiaocui2015@sina.com.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular and Nano Probes, Ministry of Education, College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China. lijing922015@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Taishan Medical College, Taian 271000, China. zwcheng95@163.com.
authors.forename: Zuowang
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Taishan Medical College, Taian 271000, China. xuyinghua1990@sina.com.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China. xiawang121@sina.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Taishan Medical College, Taian 271000, China. xrlisherry@sina.com.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nephrology, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China. xudongmei63@163.com.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Biology, Trent University, Peterborough, ON K9L0G2, Canada. ckapron@trentu.ca.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Kapron
authors.affiliation: Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China. ju.liu@sdu.edu.cn.
authors.forename: Ju
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000008:administration & dosage* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects*; D020935:MAP Kinase Signaling System; D050527:Mesangial Cells / Q000187:drug effects*
chemical_list: D004785:Environmental Pollutants; D002104:Cadmium; D048031:JNK Mitogen-Activated Protein Kinases
keywords: JNK pathway; cadmium; proliferation; renal mesangial cells