title: Histamine-induced Ca²⁺ signalling is mediated by TRPM4 channels in human adipose-derived stem cells.
abstract: Intracellular Ca2+ oscillations are frequently observed during stem cell differentiation, and there is evidence that it may control adipogenesis. The transient receptor potential melastatin 4 channel (TRPM4) is a key regulator of Ca2+ signals in excitable and non-excitable cells. However, its role in human adipose-derived stem cells (hASCs), in particular during adipogenesis, is unknown. We have investigated TRPM4 in hASCs and examined its impact on histamine-induced Ca2+ signalling and adipogenesis. Using reverse transcription (RT)-PCR, we have identified TRPM4 gene expression in hASCs and human adipose tissue. Electrophysiological recordings revealed currents with the characteristics of those reported for the channel. Furthermore, molecular suppression of TRPM4 with shRNA diminished the Ca2+ signals generated by histamine stimulation, mainly via histamine receptor 1 (H1) receptors. The increases in intracellular Ca2+ were due to influx via voltage-dependent Ca2+ channels (VDCCs) of the L-type (Ca(v)1.2) and release from the endoplasmic reticulum. Inhibition of TRPM4 by shRNA inhibited adipogenesis as indicated by the reduction in lipid droplet accumulation and adipocyte gene expression. These results suggest that TRPM4 is an important regulator of Ca2+ signals generated by histamine in hASCs and is required for adipogenesis.
authors.affiliation: *Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, U.S.A.
authors.forename: Tran Doan Ngoc
authors.initials: TD
authors.lastname: Tran
authors.affiliation: †Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX 77555, U.S.A.
authors.forename: Olga
authors.initials: O
authors.lastname: Zolochevska
authors.affiliation: †Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX 77555, U.S.A.
authors.forename: Marxa L
authors.initials: ML
authors.lastname: Figueiredo
authors.affiliation: ‡Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, U.S.A.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: ‡Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, U.S.A.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Yang
authors.affiliation: §Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, U.S.A.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.affiliation: *Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, U.S.A.
authors.forename: Shaomian
authors.initials: S
authors.lastname: Yao
authors.affiliation: *Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, U.S.A.
authors.forename: Henrique
authors.initials: H
authors.lastname: Cheng
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D006632:Histamine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D011969:Receptors, Histamine H1; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D006632:Histamine