Erratum to: Role of Potassium Channels in the Effects of Hydrogen Sulfide on Contractility of Gastric Smooth Muscle Cells in Rats

The role of the second messenger diacylglycerol (DAG) in mediating muscarinic suppression of M-current, a type of a voltage-gated K+ current that is suppressed by acetylcholine (ACh), was examined in freshly isolated smooth muscle cells from toad stomach. Currents were recorded using a single electrode voltage clamp employing conventional microelectrodes. Extracellular application of 1,2-dioctanoyl-sn-glycerol (DiC8), a synthetic DAG that is a potent activator of protein kinase C (PKC), reversibly suppressed M-current. Current relaxations, representing the voltage-dependent closure of K+ channels underlying M-current, were also decreased by DiC8, although suppression was not always as complete as it was with ACh. In contrast, another DAG analogue, 1,2-dioctanoyl-3-thioglycerol, which has a structure closely related to DiC8 but does not activate PKC, failed to inhibit M-current. Furthermore, M-current induced by the beta-agonist isoproterenol, by a mechanism apparently mediated by adenosine 3',5'-cyclic monophosphate (S. M. Sims, L. H. Clapp, J. V. Walsh, Jr., and J. J. Singer. Pflugers Arch. 417: 291, 1990), was also suppressed by DiC8. Both ACh and DiC8 were found to suppress endogenous and isoproterenol-induced M-current without altering the time course of M-current deactivation, suggesting that these agents act by decreasing the number of channels available to be opened. These results provide evidence that muscarinic regulation of M-current is mediated by DAG.

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MALAT1: A Pivotal lncRNA in the Phenotypic Switch of Gastric Smooth Muscle Cells via the Targeting of the miR-449a/DLL1 Axis in Diabetic Gastroparesis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.719581 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yanjuan Wang ◽

Yan Wang ◽

Boqian Zhu ◽

Ying Zhu ◽

Ya Jiang ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Expression Profiles ◽

Muscle Cells ◽

Diabetic Gastroparesis ◽

Luciferase Reporter ◽

Diabetic Patients ◽

Phenotypic Switch ◽

Gastric Smooth Muscle

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). Our previous study suggested that the expression of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is closely related to DGP. However, the role of MALAT1 in DGP pathogenesis remains unclear. Here, we aim to characterize the role of MALAT1 in DGP. First, we analyzed the lncRNA expression profiles through lncRNA sequencing. Next, we detected MALAT1 expression in the stomach tissues of DGP model mice and diabetic patients. Then, we investigated the role and mechanisms of MALAT1 in the proliferation, migration, phenotypic switch, and carbachol-induced intracellular Ca2+ changes in human gastric smooth muscle cells (HGSMCs) under high glucose (HG) conditions, using short hairpin RNA technology, RNA immunoprecipitation, and dual-luciferase reporter assays. We show that MALAT1 expression was upregulated in the gastric tissues of DGP model mice, the adjacent healthy tissues collected from diabetic gastric cancer patients with DGP symptoms, and in HGSMCs cultured under HG conditions. Functionally, MALAT1 knockdown in vitro impacted the viability, proliferation, migration and promoted the phenotypic switch of HGSMCs under HG conditions. Additionally, we show that MALAT1 sponged miR-449a, regulating Delta-like ligand 1 (DLL1) expression in HGSMCs; any disturbance of the MALAT1/miR-449a/DLL1 pathway affects the proliferation, migration, phenotypic switch, and carbachol-induced Ca2+ transient signals in HGSMCs under HG conditions. Collectively, our data highlight a novel regulatory signaling pathway, the MALAT1/miR-449a/DLL1 axis, in the context of DGP.

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