Evidence map›Paper›PMID 35739508›Full record

ArticleRespiratory research2022

Dysregulated myosin in Hermansky-Pudlak syndrome lung fibroblasts is associated with increased cell motility.

Jewel Imani, Steven P M Bodine, Anthony M Lamattina, Diane D Ma, Shikshya Shrestha, Dawn M Maynard, Kevin Bishop, Arinze Nwokeji, May Christine V Malicdan, Lauren C Testa and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Respiratory research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 31% of its field
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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
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

18 authors at 5 institutions in 1 country.

Jewel ImaniDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Steven P M BodineMedical Genetics Branch, NHGRI, NIH, Bethesda, MD, 20892, USA.
Anthony M LamattinaDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Diane D MaDivision of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Shikshya ShresthaDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Dawn M MaynardMedical Genetics Branch, NHGRI, NIH, Bethesda, MD, 20892, USA.
Kevin BishopZebrafish Core Facility, NHGRI, NIH, Bethesda, MD, 20892, USA.
Arinze NwokejiDivision of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
May Christine V MalicdanNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, MD, 20892, USA.
Lauren C TestaMedical Genetics Branch, NHGRI, NIH, Bethesda, MD, 20892, USA.
Raman SoodZebrafish Core Facility, NHGRI, NIH, Bethesda, MD, 20892, USA.
Benjamin StumpDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Ivan O RosasDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Mark A PerrellaDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Robert HandinDivision of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Lisa R YoungDivision of Pulmonary and Sleep Medicine, The Children's Hospital of Philadelphia, Perlman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Bernadette R GochuicoMedical Genetics Branch, NHGRI, NIH, Bethesda, MD, 20892, USA.
Souheil El-ChemalyDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. sel-chemaly@bwh.harvard.edu.
Brigham and Women's Hospital · USNational Human Genome Research Institute · USHarvard University · USOffice of the Director · USUniversity of Pennsylvania · US

Funding

Human Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6M
NHGRI/DIR Zebrafish CoreZICHG200351 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SOOD, RAMAN · 2015 to 2025
$12.1M
Mechanisms of Pulmonary Fibrosis in Hermansky-Pudlak SyndromeR01HL119503 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI YOUNG, LISA R. · 2013 to 2021
$3.6M
NHLBI NIH HHS R01 HL119503
6 · The paper itself

Abstract

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by improper biogenesis of lysosome-related organelles (LROs). Lung fibrosis is the leading cause of death among adults with HPS-1 and HPS-4 genetic types, which are associated with defects in the biogenesis of lysosome-related organelles complex-3 (BLOC-3), a guanine exchange factor (GEF) for a small GTPase, Rab32. LROs are not ubiquitously present in all cell types, and specific cells utilize LROs to accomplish dedicated functions. Fibroblasts are not known to contain LROs, and the function of BLOC-3 in fibroblasts is unclear. Here, we report that lung fibroblasts isolated from patients with HPS-1 have increased migration capacity. Silencing HPS-1 in normal lung fibroblasts similarly leads to increased migration. We also show that the increased migration is driven by elevated levels of Myosin IIB. Silencing HPS1 or RAB32 in normal lung fibroblasts leads to increased MYOSIN IIB levels. MYOSIN IIB is downstream of p38-MAPK, which is a known target of angiotensin receptor signaling. Treatment with losartan, an angiotensin receptor inhibitor, decreases MYOSIN IIB levels and impedes HPS lung fibroblast migration in vitro. Furthermore, pharmacologic inhibition of angiotensin receptor with losartan seemed to decrease migration of HPS lung fibroblasts in vivo in a zebrafish xenotransplantation model. Taken together, we demonstrate that BLOC-3 plays an important role in MYOSIN IIB regulation within lung fibroblasts and contributes to fibroblast migration.

Indexed as

Hermanski-Pudlak SyndromeAlbinismAnimalsCell MovementFibroblastsHemorrhagic DisordersHumansLosartanLungNonmuscle Myosin Type IIBReceptors, AngiotensinZebrafishLosartanNonmuscle Myosin Type IIBReceptors, AngiotensinCell migrationHermansky-Pudlak syndromeMyosin IIBPulmonary fibrosis

Identifiers

PMID35739508
PMCPMC9229912
OpenAlexW4283322486

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.