In one paragraphArticle in Circulation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
19 authors.
Asish DasguptaDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0000-0002-3670-1197 Kuang-Hueih ChenDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.
Danchen WuDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0000-0003-3901-5907 V Siddartha YerramilliDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0000-0002-4562-682X Patricia D A LimaDepartment of Medicine, Translational Institute of Medicine, and Queen's Cardiopulmonary Unit (P.D.A.L., B.P.O., T.N., C.N., O.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0000-0002-6456-2470 Ashley Y MartinDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0009-0005-8170-1638 Rachel E T BentleyDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0000-0003-0486-8467 Benjamin P OttDepartment of Medicine, Translational Institute of Medicine, and Queen's Cardiopulmonary Unit (P.D.A.L., B.P.O., T.N., C.N., O.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0009-0008-8894-3500 Tanvi NandaniDepartment of Medicine, Translational Institute of Medicine, and Queen's Cardiopulmonary Unit (P.D.A.L., B.P.O., T.N., C.N., O.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.
Jeffrey D MewburnDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0000-0002-1365-4228 Lian TianStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom (L.T.).
Ruaa Al-QazaziDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0000-0003-0983-9745 Isaac M EmonDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0009-0002-6375-1074 Pierce ColpmanDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.
Lindsay JeffersonDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0009-0009-0653-1690 Curtis NoordhofDepartment of Medicine, Translational Institute of Medicine, and Queen's Cardiopulmonary Unit (P.D.A.L., B.P.O., T.N., C.N., O.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0009-0006-5072-0585 Oliver JonesDepartment of Medicine, Translational Institute of Medicine, and Queen's Cardiopulmonary Unit (P.D.A.L., B.P.O., T.N., C.N., O.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0009-0008-6398-2052 Charles C T HindmarchDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0000-0002-6036-1292 Stephen L ArcherDepartment of Medicine (A.D., K.-H.C., D.W., V.S.Y., A.Y.M., R.E.T.B., J.D.M., R.A.-Q., I.M.E., P.C., L.J., C.C.T.H., S.L.A.), Queen's University, Kingston, ON, Canada.ORCID 0000-0003-1106-3202 Funding
No grant is acknowledged in the PubMed record.
6 · The paper itselfAbstract
backgroundDRP1 (dynamin-related protein 1) mediates mitochondrial fission and permits rapid cell cycle progression in hyperproliferative cells by coordinating nuclear and mitochondrial division, a process called mitotic fission. However, DRP1 alone appears insufficient to complete fission, and the link between fission and cell cycle progression is unknown. We hypothesize that DNM2 (dynamin 2) interacts with DRP1 to complete mitochondrial fission and regulate cell cycle progression. We show that DNM2 is upregulated in pulmonary artery smooth muscle cells (PASMCs) in human and rodent pulmonary arterial hypertension (PAH), contributing to disease pathophysiology.
methodsMitochondrial morphology, protein colocalization, and fission were assessed using stimulated emission depletion microscopy, protein interactions by immunoprecipitation, and transcriptomics by RNA sequencing. DNM2 was quantified in PASMC and lungs from patients with PAH and rats with pulmonary hypertension (PH), induced by monocrotaline or sugen5416/hypoxia. siDNM2's effects on cell proliferation, cell cycle progression, and apoptosis were assessed by flow cytometry. Single-cell RNA sequencing was performed on publicly available data sets. siDNM2 was nebulized to monocrotaline- and sugen5416/hypoxia-PH rats, and disease regression was quantified by cardiac catheterization and histology.
resultsDNM2 is increased in PAH PASMC. DNM2 interacts with DRP1 via its GTPase domain, permitting mitochondrial translocation and promoting fission. siDNM2 inhibits fission and cell proliferation and increases apoptosis. siDNM2 causes G1/G0 blockade by downregulating RGCC (regulator of cell cycle) with downstream effects on CDK (cyclin-dependent kinase) 4, cyclin D1, and p27
conclusionsDNM2 is a mediator in the terminal steps of DRP1-dependent fission and constitutes a novel therapeutic target in PAH.
Indexed as
Dynamin IIHypertension, PulmonaryMitochondrial DynamicsMitosisMyocytes, Smooth MuscleAnimalsApoptosisCell ProliferationCells, CulturedDynaminsFemaleHumansMaleMuscle, Smooth, VascularPulmonary ArteryRatsDNM2 protein, humanDynamin IIDynaminsendoplasmic reticulummitochondrial dynamicsmyocytes, smooth musclephosphorylationSTAT3 transcription factor
Identifiers
PMID42047020
PMCPMC13189384
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