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Cited 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 10.3390/biomedicines11030937PMC PMC10045937

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Abstract

Transmembrane protein 100 (TMEM100) is a crucial factor in the development and maintenance of the vascular system. The protein is involved in several processes such as angiogenesis, vascular morphogenesis, and integrity. Furthermore, TMEM100 is a downstream target of the BMP9/10 and BMPR2/ALK1 signaling pathways, which are key regulators of vascular development. Our recent studies have shown that TMEM100 is a lung endothelium enriched gene and plays a significant role in lung vascular repair and regeneration. The importance of TMEM100 in endothelial cells’ regeneration was demonstrated when Tmem100 was specifically deleted in endothelial cells, causing an impairment in their regenerative ability. However, the role of TMEM100 in various conditions and diseases is still largely unknown, making it an interesting area of research. This review summarizes the current knowledge of TMEM100, including its expression pattern, function, molecular signaling, and clinical implications, which could be valuable in the development of novel therapies for the treatment of cardiovascular and pulmonary diseases.

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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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Citations

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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
2023-03-17
Volume
11
Issue
3
Pages
937
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines11030937
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
  • NIH (R00HL138278, R01HL158596, 20CDA35310084, RFGA2022-010-06)
  • AHA Career Development Award (R00HL138278, R01HL158596, 20CDA35310084, RFGA2022-010-06)
  • The Cardiovascular Medical and Education Fund (R00HL138278, R01HL158596, 20CDA35310084, RFGA2022-010-06)
  • University of Arizona Startup (R00HL138278, R01HL158596, 20CDA35310084, RFGA2022-010-06)
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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