Deleting the TGF-β receptor in proximal tubules impairs HGF signaling

Khodo, Stellor Nlandu; Neelisetty, Surekha; Woodbury, Luke; Green, Elizabeth; Harris, Raymond C.; Zent, Roy; Gewin, Leslie

doi:10.1152/ajprenal.00446.2015

Cited by 10 publications

(2 citation statements)

References 40 publications

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“…Transforming growth factor b (TGF-b) type II receptor conditionally deficient murine proximal tubule cells were the generous gift of Dr. Leslie Gewin. 16 Murine cells were maintained in DMEM/F-12 medium with supplements. For most hydrogel experiments, 100k low passage (P1-P4) human primary renal tubule epithelial cells were seeded per well, on either soft (0.5-1.0 kPa) or stiff (40-50 kPa) hydrogels in six-well plates.…”

Section: Cell Culturementioning

confidence: 99%

Substrate Elasticity Governs Differentiation of Renal Tubule Cells in Prolonged Culture

Love

Jorgensen

et al. 2019

Tissue Engineering Part A

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End-stage renal disease afflicts *750,000 Americans and claims >100,000 lives annually in the United States. Kidney transplantation is associated with longest survival and least cost but is limited by scarcity of donor organs. The balance of patients are treated with dialysis, a cumbersome, morbid, and expensive procedure. Each hemodialysis treatment consumes in excess of 160 liters of water and anchors the patient to a machine for 12-15 h per week. Cultured tubule cells can reduce the obligate fluid requirements of a bioengineered artificial kidney by concentrating wastes and reabsorbing filtered salt and water. Primary tubule epithelial cells rapidly dedifferentiate in culture and form a flattened epithelium lacking the brush border essential to apicobasal transport. We hypothesized that substrate mechanical properties have a strong influence on differentiation in primary cell culture. We cultured primary renal tubule cells on polyacrylamide hydrogels of varying elasticity and measured expression of key transporter proteins essential to renal tubule cell function. Primary tubule cells cultured on soft substrates for extended periods showed increased expression of key transporters characteristic of differentiated proximal tubule cells. These data support the hypothesis that scaffold elasticity is a critical factor in cell culture, and, unexpectedly, that prolonged culture of primary cells was essential to observing this difference.

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Section: Cell Culturementioning

confidence: 99%

Substrate Elasticity Governs Differentiation of Renal Tubule Cells in Prolonged Culture

Love

Jorgensen

et al. 2019

Tissue Engineering Part A

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, TGF-β1 induces a dose-dependent inhibition of endothelial cord formation and modulation of endothelial VEGFR2 expression in an ALK5-dependent fashion [ 30 ]. Finally, several studies reveal that hepatocyte growth factor (HGF)/MET signaling axis antagonizes the profibrotic actions of TGF-β1 by intercepting SMAD signal transduction through diverse mechanisms [ 31 , 32 , 33 ]. In addition, TGF-β1/ALK5 and HGF/Met negatively regulate each other’s production during kidney injury [ 34 ].…”

Section: Par2 and Tgf-βmentioning

confidence: 99%

Proteinase-Activated Receptor 2 May Drive Cancer Progression by Facilitating TGF-β Signaling

Ungefroren

Witte

Rauch

et al. 2017

IJMS

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The G protein-coupled receptor proteinase-activated receptor 2 (PAR2) has been implicated in various aspects of cellular physiology including inflammation, obesity and cancer. In cancer, it usually acts as a driver of cancer progression in various tumor types by promoting invasion and metastasis in response to activation by serine proteinases. Recently, we discovered another mode through which PAR2 may enhance tumorigenesis: crosstalk with transforming growth factor-β (TGF-β) signaling to promote TGF-β1-induced cell migration/invasion and invasion-associated gene expression in ductal pancreatic adenocarcinoma (PDAC) cells. In this chapter, we review what is known about the cellular TGF-β responses and signaling pathways affected by PAR2 expression, the signaling activities of PAR2 required for promoting TGF-β signaling, and the potential molecular mechanism(s) that underlie(s) the TGF-β signaling–promoting effect. Since PAR2 is activated through various serine proteinases and biased agonists, it may couple TGF-β signaling to a diverse range of other physiological processes that may or may not predispose cells to cancer development such as local inflammation, systemic coagulation and pathogen infection.

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miR‐26a modulates HGF and STAT3 effects on the kidney repair process in a glycerol‐induced AKI model in rats

Gattai

Maquigussa

Novaes

et al. 2018

J of Cellular Biochemistry

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Acute kidney injury is mostly reversible, and hepatocyte growth factor (HGF) has a relevant role in the tissue repair. MicroRNA (miR)-26a is an endogenous modulator of HGF. The role of miR-26a in the kidney repair process was evaluated in Wistar rats submitted to an acute kidney injury model of rhabdomyolysis induced by glycerol (6 mL/kg). Animals were evaluated 3, 12, 48, 96, and 120 hours after glycerol injection. Serum creatinine (SCr) and gene expression of HGF, c-met, signal transducer and activator of transcription 3 (STAT3), and miR-26a were estimated. Also, tubular NK52E cells were transfected with anti-miR26a and stimulated with Fe 3+ for 24 hours to mimic the effects of myoglobin in vitro. SCr was highest after 48 hours. After 96 hours, SCr started to decrease, characterizing the recovery phase, with normalization after 120 hours. HGF expression increased during the onset phase (3 hours), with a low relationship with miR-26a. In contrast, in the recovery phase, the increase in miR-26a was coincident with HGF messenger RNA suppression, suggesting that in the recovery phase, miR-26a may have a role in HGF modulation. Fe 3+ induced cellular death after 3 hours and proliferation after 24 hours. There was no correlation between miR-26a and STAT3 during the death phase; however, during the proliferation phase, an increase in STAT3 was paralleled with a decrease in miR-26a. miR-26a silencing induced increases in cell viability and the phosphorylated form of STAT3 protein expression in cells receiving Fe 3+ . In conclusion, miR-26a may have a key role in modulating HGF levels after its proliferative effects have been triggered.

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Deleting the TGF-β receptor in proximal tubules impairs HGF signaling

Cited by 10 publications

References 40 publications

Substrate Elasticity Governs Differentiation of Renal Tubule Cells in Prolonged Culture

Substrate Elasticity Governs Differentiation of Renal Tubule Cells in Prolonged Culture

Proteinase-Activated Receptor 2 May Drive Cancer Progression by Facilitating TGF-β Signaling

miR‐26a modulates HGF and STAT3 effects on the kidney repair process in a glycerol‐induced AKI model in rats

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