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PreprintCited by 14Angiogenesis and VEGF in CancerPulmonary Hypertension Research and TreatmentsTGF-β signaling in diseases

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The Role of a Lung Vascular Endothelium Enriched Gene TMEM100

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Pan, JiaKai, Liu, Bin, Dai, Zhiyu·2023·Biomedicines
DOI 10.20944/preprints202302.0337.v1PMC PMC10045937

Preprint — published as 10.3390/biomedicines11030937 · Paper page

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Abstract

Transmembrane protein 100 (TMEM100) plays an important role in angiogenesis, vascular morphogenesis, integrity and cardiovascular development. TMEM100 is a downstream target of the BMP9/10 and BMPR2/ALK1 signaling pathways. Our recent study demonstrates TMEM100 is a lung endothelium enriched gene. Endothelial-specific deletion of Tmem100 impairs lung endothelial cells regeneration. Activation of Tmem100 signaling represents a novel strategy for lung vascular repair and regeneration. It is interesting and important to understand the roles of TMEM100 in the physiological and pathological conditions. In this review, we summarized the current knowledge of TMEM100.

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Crossref · 10.20944/preprints202302.0337.v1

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Figures

Figure 1 TMEM100. (A) The diagram of AlphaFold prediction of TMEM100. TM: transmembrane domain. YSFNSHGSI indicates the putative extracellular domain of TMEM100. (B) Amino acid sequences of TMEM100 from multiple species. Boxes represent two putative transmembrane (TM) domains. Residues conserved with the human sequence are shaded in gray. Reproduction from ref. [10].
Figure 1 TMEM100. (A) The diagram of AlphaFold prediction of TMEM100. TM: transmembrane domain. YSFNSHGSI indicates the putative extracellular domain of TMEM100. (B) Amino acid sequences of TMEM100 from multiple species. Boxes represent two putative transmembrane (TM) domains. Residues conserved with the human sequence are shaded in gray. Reproduction from ref. [10].CC BY · PubMed Central
Figure 2 Role of TMEM100. TMEM100 is a two transmembrane protein located in the plasma membrane and endoplasmic reticulum membrane. TMEM100 is a BMP9/10-BMPR2/ALK1-pSMAD1/5/8 signaling downstream target. Various factors such as VEGF, PEG11/RGL1, GATA5, Calcium signaling and ATF6α upregulate TMEM100 expression. Inflammatory cytokines such as TNF-α, miR421/miR106, and HDAC6 suppress TMEM100 expression. TMEM100 has been demonstrated to positively regulate NOTCH, MFAP4, and E2F1 signaling, and inhibit JNK/ERK, β-catenin, TGF-β signaling. Our unpublished data showed that hypoxia and inflammatory injury reduce TMEM100 expression in the lung ECs, whereas VEGF upregulates TMEM100 expression. (indicated by dotted lines).
Figure 2 Role of TMEM100. TMEM100 is a two transmembrane protein located in the plasma membrane and endoplasmic reticulum membrane. TMEM100 is a BMP9/10-BMPR2/ALK1-pSMAD1/5/8 signaling downstream target. Various factors such as VEGF, PEG11/RGL1, GATA5, Calcium signaling and ATF6α upregulate TMEM100 expression. Inflammatory cytokines such as TNF-α, miR421/miR106, and HDAC6 suppress TMEM100 expression. TMEM100 has been demonstrated to positively regulate NOTCH, MFAP4, and E2F1 signaling, and inhibit JNK/ERK, β-catenin, TGF-β signaling. Our unpublished data showed that hypoxia and inflammatory injury reduce TMEM100 expression in the lung ECs, whereas VEGF upregulates TMEM100 expression. (indicated by dotted lines).CC BY · PubMed Central

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Metadata

Authors
Pan, J., Liu, B., & Dai, Z.
Affiliations
University of Arizona (US)
Corresponding author
Dai, Zhiyu
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2023-02-20
Volume
11
Issue
3
Pages
937-937
ISSN
2227-9059 (ISSN-L)
DOI
10.20944/preprints202302.0337.v1
PMC
PMC10045937
OpenAlex
W4327944883
Cited by
14
References
1
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 3
FWCI
0.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Heart Association (R00HL138278, RFGA2022-010-06, R01HL158596, 20CDA35310084)
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R00HL138278, R01HL158596)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
TMEM100, lung endothelium, re-endothelialization, vascular development, lung disease, cardiovascular disease

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