{"doi":"10.1159/000430161","title":"Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells","abstract":"<jats:p>Background and Aims: There is accumulating evidence that sympathetic nervous hyperactivity contributes to the pathogenesis of glomerular sclerosis independent of blood pressure effects. A previous study showed that α1-adrenoceptor (α1-AR) antagonists inhibit mesangial cell (MC) proliferation. However, the underlying mechanism remains unclear. Methods and Results: We found that α1-AR is expressed in a human mesangial cell line. The α1-AR agonist phenylephrine (PE) induced Ca2+ influx as well as release from intracellular Ca2+ stores. Blockade of TRPC6 with siRNA, anti-TRPC6 antibodies and a TRPC blocker attenuated the PE-induced [Ca2+]i increase. Additionally, the PE-induced [Ca2+]i increase was phospholipase C dependent. Furthermore, PE induced a [Ca2+]i increase even when the intracellular Ca2+ stores were already depleted. This effect was mimicked by an analog of diacylglycerol. These results suggested that, upon α1-AR stimulation, TRPC6 mediates Ca2+ influx via a receptor-operated Ca2+ entry mechanism. Finally, TRPC6 contributes to the PE-induced MC proliferation. The mechanisms are associated with the extracellular signal-regulated kinase (ERK) signaling pathway because blockade of TRPC6 and chelation of extracellular Ca2+ abrogated PE-induced ERK1/2 abrogated PE-induced ERK1/2 phosphorylation. Conclusion: TRPC6 channels are involved in α1-AR activation-induced Ca2+ entry, which mediates proliferation via ERK signaling in human MCs</jats:p>","journal":"Cellular Physiology and Biochemistry","year":2015,"id":26127,"datarank":1.32191037768425,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.8220797011579694,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.8220797011579694,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":26,"citers_with_citation_signal":26,"citers_with_endowment":26,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":151868,"name":"Linlin Ma","orcid":null,"position":1,"is_corresponding":false},{"id":151869,"name":"Li Zou","orcid":null,"position":2,"is_corresponding":false},{"id":151870,"name":"Kexin Meng","orcid":null,"position":3,"is_corresponding":false},{"id":151871,"name":"Tianrong Ji","orcid":null,"position":4,"is_corresponding":false},{"id":17693,"name":"Lei Zhang","orcid":"0000-0003-4921-8986","position":5,"is_corresponding":false},{"id":32765,"name":"Rui Zhang","orcid":"0000-0001-9000-5021","position":6,"is_corresponding":false},{"id":151872,"name":"Jundong Jiao","orcid":null,"position":7,"is_corresponding":false},{"id":151867,"name":"Fanwu Kong","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.332204510175204,"endowment":3.332204510175204,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26202353","pmcid":null,"openalex_id":"https://openalex.org/W1529707635","authors":[],"funders":[],"total_grants":0,"fwci":2.4062,"citation_percentile":0.8701547,"influential_citations":2,"citation_trend":[{"year":2015,"count":1},{"year":2016,"count":4},{"year":2017,"count":5},{"year":2018,"count":4},{"year":2019,"count":2},{"year":2020,"count":1},{"year":2021,"count":2},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1159/000430161","host_type":"journal"},{"url":"https://doi.org/10.1159/000430161","host_type":"GOLD"},{"url":"https://doi.org/10.1159/000430161","host_type":"publisher"},{"url":"https://www.karger.com/Article/Pdf/430161","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26202353","host_type":"repository"},{"url":"https://doaj.org/article/ad96e13b27404ea88c4303d4c9aad102","host_type":"repository"}],"fields_of_study":["Ion Channels and Receptors","Renal Diseases and Glomerulopathies","Receptor Mechanisms and Signaling","Medicine","Chemistry","Adrenergic alpha-Agonists","Calcium","Cell Line","Cell Proliferation","Glomerular Mesangium","Humans","Ion Transport","MAP Kinase Signaling System","Receptors, Adrenergic, alpha-1","TRPC Cation Channels","TRPC6 Cation Channel"],"mesh_terms":["TRPC6 Cation Channel","Adrenergic alpha-Agonists","Calcium","Cell Line","Glomerular Mesangium","Humans","Ion Transport","Receptors, Adrenergic, alpha-1","MAP Kinase Signaling System","Cell Proliferation","TRPC Cation Channels"],"keywords":["TRPC6","TRPC","Cell biology","Extracellular","Intracellular","Phospholipase C","Signal transduction","MAPK/ERK pathway","Mesangial cell","Endocrinology","TRPC3","Calcium in biology","Protein kinase C","Internal medicine","Agonist","Thapsigargin","Receptor","Chemistry","Biology","Transient receptor potential channel","Medicine","Kidney"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T11:49:42.559791Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}