Evidence map›Paper›PMID 40661447›Full record

ArticlebioRxiv : the preprint server for biology2025

The mitochondrial unfolded protein response and metabolic reprogramming promote PASMC proliferation in response to sphingosine kinase-1/sphingosine-1-phosphate signaling.

Angelia D Lockett, Aaron Snow, Pontian Adogamhe, Justin Sysol, Manas Yadav, Tendo Mubuuke, Marta T Gomes, Todd Cook, Amanda Fisher, Micheala A Aldred and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Angelia D LockettDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Aaron SnowDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Pontian AdogamheDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Justin SysolDepartment of Medicine, University of Rochester Medical Center.
Manas YadavDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Tendo MubuukeDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Marta T GomesDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Todd CookDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Amanda FisherDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Micheala A AldredDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Roberto F MachadoDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

Funding

Pulmonary Hypertension Breakthrough InitiativeR24HL123767 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ALDRED, MICHEALA A, ERZURUM, SERPIL C. · 2014 to 2017
$10.1M
Genomics of Pulmonary Vascular DiseaseR35HL140019 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI ALDRED, MICHEALA A · 2018 to 2024
$5.6M
Role of Sphingolipid Pathways in the Pathobiology of PAHR01HL127342 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MACHADO, ROBERTO F., NATARAJAN, VISWANATHAN · 2016 to 2023
$4.5M
PRIDE Academy: Impact of Ancestry and Gender to omics of lung diseasesR25HL146166 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Matthew Wayne DeCamp, Sonia Castro Flores · 2019 to 2026
$3.4M
NAD-dependent Signaling and Pulmonary Vascular Remodeling in PAHR01HL158108 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI MACHADO, ROBERTO F. · 2022 to 2025
$2.9M
Regulation of UPRmt activation in the development of pulmonary vascular remodeling in PAHK01HL164874 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI LOCKETT, ANGELIA DENISE · 2022 to 2024
$336k
NHLBI NIH HHS K01 HL164874NHLBI NIH HHS R01 HL127342NHLBI NIH HHS R01 HL158108NHLBI NIH HHS R24 HL123767NHLBI NIH HHS R25 HL146166NHLBI NIH HHS R35 HL140019
6 · The paper itself

Abstract

Proliferation and vasoconstriction of the intimal smooth muscle layer of the pulmonary artery are pathogenic characteristics of pulmonary arterial hypertension (PAH). Altered mitochondrial function, i.e. glycolysis, ROS generation and fission, are known potentiators of vascular remodeling. However, most current therapeutic interventions fail to effectively address the proliferation of the pulmonary artery smooth muscle cells (PASMCSs) lining the pulmonary vasculature and highlight the importance of identifying novel pathways to target for intervention. The Sphk1/S1P/S1P2 signaling axis is upregulated in PAH patients and is known to induce PASMC proliferation during hypoxia-mediated pulmonary hypertension (HPH). Interestingly, Sphk1 modulates mitochondrial function in that it regulates dynamics, cell growth and survival and in

Identifiers

PMID40661447
PMCPMC12259073

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.