Transmembrane protein 215 promotes angiogenesis by maintaining endothelial cell survival

Abstract

Sprouting angiogenesis is a major form of neovascularization of tissues suffering from hypoxia and other related stress. Endothelial cells (ECs) undergo proliferation, differentiation, programmed death, and migration during angiogenic sprouting, but the underlying molecular mechanisms regulating ECs in angiogenesis have been incompletely elucidated. Here we report that the transmembrane protein 215 (TMEM215) is involved in angiogenesis by regulating EC survival. The murine TMEM215 gene, which possesses two transcriptional starting sites as determined by 5′‐rapid amplification of complementary DNA (cDNA) ends (RACE), encodes a two‐pass TMEM. The TMEM215 transcripts were detected in ECs in addition to other tissues by quantitative reverse transcription‐polymerase chain reaction. Immunofluorescence showed that TMEM215 was expressed in the vasculature in retina, liver, and tumor, and colocalized with EC markers. We show that knockdown of TMEM215 in ECs induced strong cell death of ECs in vitro without affecting cell proliferation and migration, suggesting that TMEM215 was required for EC survival. Downregulation of TMEM215 expression compromised lumen formation and sprouting capacities of ECs in vitro. Moreover, intravitreous injection of TMEM215 small interfering RNA resulted in delayed and abnormal development of retinal vasculature with poor perfusion. These results identified TMEM215 as a novel molecule involved in angiogenesis by regulating the survival of ECs.

Molecular identity of the lateral lemniscus nuclei in the adult mouse brain

“…Kcnh7 is a potassium voltage-gated channel that would be a good candidate to be responsible for DFNA16, like the aforementioned KCNQ4 , and KCNQ1 and KCNE1 potassium channels that when mutated result in Jervell and Lange-Nielsen cardioauditory syndrome ( Neyroud et al, 1997 ; Schulze-Bahr et al, 1997 ). Concerning, Tmem215 , it codes for a transmembrane protein involved in the survival of endothelial cells ( Liu et al, 2019 ), although its possible involvement in the auditory system would need to be analyzed.…”

TMEM205 Reduces the Sensitivity of Gastric Cancer to Cisplatin Through TAM/M2 Polarization

“…TMEM107 affected the proliferation, migration, and EMT process of NSCLC cells [6] . Knocking down TMEM215 inhibited the angiogenesis of HUVECs [7] . TMEM119 enhanced stemness of breast cancer cells by activating the Wnt/β-catenin signaling pathway [8] .…”

Early Treatment With a Single Dose of Mesenchymal Stem Cell Derived Extracellular Vesicles Modulates the Brain Transcriptome to Create Neuroprotective Changes in a Porcine Model of Traumatic Brain Injury and Hemorrhagic Shock

“…In addition, TMEM215 was one of the most highly upregulated genes. This transmembrane protein has recently been implicated in angiogenesis by promoting endothelial cell survival (48). Angiogenesis is thought to play an important role in neovascularization that is vital to long-term neurorestoration following TBI (49).…”