Transgelin induces dysfunction of fetal endothelial colony-forming cells from gestational diabetic pregnancies

Varberg, Kaela M.; Garretson, Rashell O.; Blue, Emily K.; Chu, Chenghao; Gohn, Cassandra R.; Tu, Wanzhu; Haneline, Laura S.

doi:10.1152/ajpcell.00137.2018

Cited by 18 publications

(38 citation statements)

References 40 publications

(67 reference statements)

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“…Transgelins are a family of proteins that were discovered decades ago ( Lees-Miller et al, 1987 ; Shapland et al, 1993 ). They are involved in many diseases, including asthma, hypertension, diabetes and cancer, but the role of transgelins in cancer is not very clear ( Huang et al, 2018 ; Sun et al, 2018 ; Varberg et al, 2018 ; Yin et al, 2018 ). Recently, studies have shown that transgelins are associated with CRC metastasis.…”

Section: Introductionmentioning

confidence: 99%

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

Zhang

et al. 2020

Front. Cell Dev. Biol.

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Transgelins, including transgelin-1 (T-1), transgelin-2 (T-2), and transgelin-3 (T-3), are a family of actin-binding proteins (ABPs) that can alter the structure and morphology of the cytoskeleton. These proteins function by regulating migration, proliferation and apoptosis in many different cancers. Several studies have shown that in various types of tumor cells, including colorectal cancer (CRC) cells, and in the tumor microenvironment, the expression and biological effects of transgelins are diverse and may transform during tumor progression. Previous researches have demonstrated that transgelin levels are positively correlated with metastasis in CRC, and down-regulating their expression can inhibit this process. In advanced disease, T-1 is a tumor activator with increasing expression, and T-2 expression increases with the progression of CRC. Finally, T-3 is only expressed in neurons and is not associated with CRC. This evidence suggests that T-1 and T-2 are potential biomarkers and therapeutic targets for CRC metastasis.

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Section: Introductionmentioning

confidence: 99%

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

Zhang

et al. 2020

Front. Cell Dev. Biol.

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“…Both proteins (TAGLN and MGP) are expressed in smooth muscle cells of developing vasculature and most likely contribute to vasculogenic dysfunction of PE. 21 , 25 , 26 Similar to MGP and TAGLN, the differentially upregulated HSPG2 protein is also associated with vascularity. This extracellular matrix protein has an active role in vascular homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid of Preeclamptic and Normotensive Pregnant Women Compared to Nonpregnant Women Analyzed with Mass Spectrometry

et al. 2020

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Preeclampsia is a pregnancy-specific multiorgan disorder in which impaired placental functioning and excessive oxidative stress play an important role. We previously showed distinct differences between cerebrospinal fluid proteins in patients with preeclampsia and normotensive pregnant women. An additional group of nonpregnant women was included to study the presence of pregnancy-related proteins in normotensive and preeclamptic pregnancies and whether pregnancy-related proteins were associated with preeclampsia. Cerebrospinal fluid samples were tryptically digested and subsequently measured with a nano-LC-tribrid Orbitrap mass spectrometry system. Proteins were identified by shotgun proteomic analysis based on a data-dependent acquisition method. Proteins identified in preeclampsia, normotensive pregnant controls, and nonpregnant groups were compared to the Progenesis method according to the criteria as previously described and with a secondary analysis using a Scaffold method including Benjamini–Hochberg correction for multiple testing. For preeclampsia, the Progenesis and the Scaffold method together identified 15 (eight proteins for both analyses with one overlap) proteins that were significantly different compared to normotensive control pregnancies. Three of these 15 proteins, which were elevated in cerebrospinal fluid of preeclamptic women, were described to be pregnancy proteins with a calcium-binding function. Using two analysis methods (Progenesis and Scaffold), four out of 15 differential proteins were associated with pregnancy, as described in the literature. Three out of the four pregnancy-related proteins were elevated in preeclampsia. Furthermore, the contribution of elevated ( n = 4/15) and downregulated ( n = 2/15) calcium-binding proteins in preeclampsia is remarkably high (40%) and needs to be elucidated further.

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“…Primary Human Endothelial Colony Formation Cells (ECFCs) were generously provided by Dr. Laura Haneline (IUSM). ECFCs were isolated from umbilical cord blood samples by the Indiana University Simon Cancer Center Angio BioCore and stored as previously described 66 . ECFC aliquots were thawed and cultured in endothelial growth media 2 (EGM2, Lonza America, Inc., Walkersille, MD) plus 10% FBS, plated on flasks coated with type 1 collagen (Corning, Inc., Durham, NC).…”

Section: Cell Culture Of Cell Lines and Primary Human Endothelial Colmentioning

confidence: 99%

Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23

Mulcrone

Edwards

Petrusca

et al. 2020

Sci Rep

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Multiple Myeloma (MM) induces bone destruction, decreases bone formation, and increases marrow angiogenesis in patients. We reported that osteocytes (Ocys) directly interact with MM cells to increase tumor growth and expression of Ocy-derived factors that promote bone resorption and suppress bone formation. However, the contribution of Ocys to enhanced marrow vascularization in MM is unclear. Since the MM microenvironment is hypoxic, we assessed if hypoxia and/or interactions with MM cells increases pro-angiogenic signaling in Ocys. Hypoxia and/or co-culture with MM cells significantly increased Vegf-a expression in MLOA5-Ocys, and conditioned media (CM) from MLOA5s or MM-MLOA5 co-cultured in hypoxia, significantly increased endothelial tube length compared to normoxic CM. Further, Vegf-a knockdown in MLOA5s or primary Ocys co-cultured with MM cells or neutralizing Vegf-a in MM-Ocy co-culture CM completely blocked the increased endothelial activity. Importantly, Vegf-a-expressing Ocy numbers were significantly increased in MM-injected mouse bones, positively correlating with tumor vessel area. Finally, we demonstrate that direct contact with MM cells increases Ocy Fgf23, which enhanced Vegf-a expression in Ocys. Fgf23 deletion in Ocys blocked these changes. These results suggest hypoxia and MM cells induce a pro-angiogenic phenotype in Ocys via Fgf23 and Vegf-a signaling, which can promote MM-induced marrow vascularization.

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Transgelin induces dysfunction of fetal endothelial colony-forming cells from gestational diabetic pregnancies

Cited by 18 publications

References 40 publications

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

Cerebrospinal Fluid of Preeclamptic and Normotensive Pregnant Women Compared to Nonpregnant Women Analyzed with Mass Spectrometry

Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23

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