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BKCa Mediates Dysfunction in High Glucose Induced Mesangial Cell Injury via TGF-?1/Smad2/3 Signaling Pathways.

ABSTRACT: Objective:To explore the role and mechanism of BKCa in diabetic kidney disease. Methods:Rat mesangial cells (MCs) HBZY-1 were cultured with high glucose to simulate the high-glucose environment of diabetic kidney disease in vivo. The effects of large conductance calcium-activated potassium channel (BKCa) on proliferation, migration, and apoptosis of HBZY-1 cells were observed. The contents of transforming growth factor beta 1 (TGF-?1), Smad2/3, collagen IV (Col IV), and fibronectin (FN) in the extracellular matrix were also observed. Results:High glucose significantly damaged HBZY-1 cells, which enhanced the ability of cell proliferation, migration, and apoptosis, and increased the secretion of Col IV and FN. Inhibition of BKCa and TGF-?1/Smad2/3 signaling pathways can inhibit the proliferation, migration, and apoptosis of HBZY-1 cells and suppress the secretion of Col IV and FN. The effect of excitation is the opposite. Conclusions:BKCa regulates mesangial cell proliferation, migration, apoptosis, and secretion of Col IV and FN and is associated with TGF-?1/Smad2/3 signaling pathway.

SUBMITTER: Wu Z

PROVIDER: S-EPMC7206888 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

BK<sub>Ca</sub> Mediates Dysfunction in High Glucose Induced Mesangial Cell Injury via TGF-<i>β</i>1/Smad2/3 Signaling Pathways.

Wu Zhigui Z Yin Wenxian W Sun Mengqi M Si Yuankai Y Wu Xiaoxiao X Chen Meijuan M

International journal of endocrinology 20200429

<h4>Objective</h4>To explore the role and mechanism of BK<sub>Ca</sub> in diabetic kidney disease.<h4>Methods</h4>Rat mesangial cells (MCs) HBZY-1 were cultured with high glucose to simulate the high-glucose environment of diabetic kidney disease in vivo. The effects of large conductance calcium-activated potassium channel (BK<sub>Ca</sub>) on proliferation, migration, and apoptosis of HBZY-1 cells were observed. The contents of transforming growth factor beta 1 (TGF-<i>β</i>1), Smad2/3, collage ...[more]

PMID: 32411221

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Project description:Mammalian circadian (24 h) rhythms are timed by the pattern of spontaneous action potential firing in the suprachiasmatic nucleus (SCN). This oscillation in firing is produced through circadian regulation of several membrane currents, including large-conductance Ca2+- and voltage-activated K+ (BK) and L-type Ca2+ channel (LTCC) currents. During the day steady-state BK currents depend mostly on LTCCs for activation, whereas at night they depend predominantly on ryanodine receptors (RyRs). However, the contribution of these Ca2+ channels to BK channel activation during action potential firing has not been thoroughly investigated. In this study, we used a pharmacological approach to determine that both LTCCs and RyRs contribute to the baseline membrane potential of SCN action potential waveforms, as well as action potential-evoked BK current, during the day and night, respectively. Since the baseline membrane potential is a major determinant of circadian firing rate, we focused on the LTCCs contributing to low voltage activation of BK channels during the subthreshold phase. For these experiments, two LTCC subtypes found in SCN (CaV1.2 and CaV1.3) were coexpressed with BK channels in heterologous cells, where their differential contributions could be separately measured. CaV1.3 channels produced currents that were shifted to more hyperpolarized potentials compared with CaV1.2, resulting in increased subthreshold Ca2+ and BK currents during an action potential command. These results show that although multiple Ca2+ sources in SCN can contribute to the activation of BK current during an action potential, specific BK-CaV1.3 partnerships may optimize the subthreshold BK current activation that is critical for firing rate regulation.NEW & NOTEWORTHY BK K+ channels are important regulators of firing. Although Ca2+ channels are required for their activation in excitable cells, it is not well understood how BK channels activate using these Ca2+ sources during an action potential. This study demonstrates the differences in BK current activated by CaV1.2 and CaV1.3 channels in clock neurons and heterologous cells. The results define how specific ion channel partnerships can be engaged during distinct phases of the action potential.

Dataset Information

BKCa Mediates Dysfunction in High Glucose Induced Mesangial Cell Injury via TGF-?1/Smad2/3 Signaling Pathways.

Publications

BK<sub>Ca</sub> Mediates Dysfunction in High Glucose Induced Mesangial Cell Injury via TGF-<i>β</i>1/Smad2/3 Signaling Pathways.

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