Human proximal tubular epithelial cells express somatostatin: regulation by growth factors and cAMP

Somatostatin modulates several renal tubular cell functions, including gluconeogenesis and proliferation. In this study, we demonstrate that cultured human proximal tubular epithelial cells (PTEC) express somatostatin. We also demonstrate positive and negative regulation of PTEC somatostatin production. We found that PTEC derived from 14 different human donors consistently expressed somatostatin mRNA and/or peptide as detected by RT-PCR and enzyme-linked immunoassay. Furthermore, Northern blot analysis revealed that PTEC express the same size mRNA transcript (750 nucleotides) as human thyroid carcinoma (TT) cells. The PTEC mitogens, epidermal growth factor (EGF) and hydrocortisone, inhibit PTEC somatostatin secretion, whereas forskolin (a direct stimulator of adenylate cyclase) and fetal bovine serum stimulate secretion. These findings raise the possibility that renal-derived somatostatin modulates tubular cell function in an autocrine/paracrine manner. Manipulation of this pathway may lead to novel methods with which to alter tubular cell proliferation and function in vivo.

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Mitochondria transfer from mesenchymal stem cells structurally and functionally repairs renal proximal tubular epithelial cells in diabetic nephropathy in vivo

Scientific Reports ◽

10.1038/s41598-019-40163-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 20

Author(s):

Naoto Konari ◽

Kanna Nagaishi ◽

Shin Kikuchi ◽

Mineko Fujimiya

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Diabetic Nephropathy ◽

Epithelial Cells ◽

Tubular Epithelial Cells ◽

Mitochondria Transfer ◽

Proximal Tubular Epithelial Cells ◽

Proximal Tubular ◽

Renal Proximal Tubular

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Long term safety of targeted internalization of cell penetrating peptide crotamine into renal proximal tubular epithelial cells in vivo

Scientific Reports ◽

10.1038/s41598-019-39842-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Joana Darc Campeiro ◽

Wendy Dam ◽

Gabriela Guilherme Monte ◽

Lucas Carvalho Porta ◽

Lilian Caroline Gonçalves de Oliveira ◽

...

Keyword(s):

Epithelial Cells ◽

Cell Penetrating Peptide ◽

Tubular Epithelial Cells ◽

Cell Penetrating ◽

Proximal Tubular Epithelial Cells ◽

Proximal Tubular ◽

Renal Proximal Tubular

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Early upregulation of iNOS mRNA expression and increase in NO metabolites in pressurized renal epithelial cells

AJP Renal Physiology ◽

10.1152/ajprenal.00238.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. F1877-F1888 ◽

Cited By ~ 23

Author(s):

Nalini V. Broadbelt ◽

Peter J. Stahl ◽

Jie Chen ◽

Moshe Mizrahi ◽

Amit Lal ◽

...

Keyword(s):

Epithelial Cells ◽

Critical Factor ◽

Nuclear Factor Κb ◽

Inos Mrna ◽

Tubular Epithelial Cells ◽

Inos Inhibitor ◽

Progression Of Disease ◽

Proximal Tubular Epithelial Cells ◽

Proximal Tubular

Pressure is an important physiological regulator, but under abnormal conditions it may be a critical factor in the onset and progression of disease in many organs. In vivo, proximal tubular epithelial cells are subjected to pressure as a result of ureteral obstruction, which may influence the production of nitric oxide (NO), a ubiquitous multifunctional cytokine. To directly explore the effect of pressure on the expression and activity of NO synthase (NOS) in cultured proximal tubular epithelial cells, a novel pressure apparatus was developed. Cells were subjected to pressures of 20–120 mmHg over time (5 min-72 h). RT-PCR demonstrated an increase in inducible NOS (iNOS) and sGC, while endothelial NOS remained unchanged. Real-time PCR (qPCR) confirmed an earlier induction of iNOS transcript subjected to 60 mmHg compared with cytokine mix. iNOS protein expression was significantly increased following 60 mmHg of pressure for 24 h. Use of nuclear factor-κB inhibitors was shown to prevent the increase in iNOS expression following 60 mmHg for 2 h. NO and cGMP were increased with the application of pressure. The addition of the irreversible iNOS inhibitor (1400W) was shown to prevent this increase. We demonstrate that with the use of a simply designed apparatus, pressure led to an extremely early induction of iNOS and a rapid activation of NOS activity to increase NO and cGMP in proximal tubule epithelial cells. The rapid effects of pressure on iNOS may have important implications in the obstructed kidney.

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Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells

Scientific Reports ◽

10.1038/s41598-021-94185-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Timo N. Haschler ◽

Harry Horsley ◽

Monika Balys ◽

Glenn Anderson ◽

Jan-Willem Taanman ◽

...

Keyword(s):

Epithelial Cells ◽

Mitochondrial Function ◽

Kidney Injury ◽

Tubular Epithelial Cells ◽

Atp Production ◽

Form And Function ◽

Proximal Tubular Epithelial Cells ◽

Proximal Tubular

AbstractIschemia is a major cause of kidney damage. Proximal tubular epithelial cells (PTECs) are highly susceptible to ischemic insults that frequently cause acute kidney injury (AKI), a potentially life-threatening condition with high mortality. Accumulating evidence has identified altered mitochondrial function as a central pathologic feature of AKI. The mitochondrial NAD+-dependent enzyme sirtuin 5 (SIRT5) is a key regulator of mitochondrial form and function, but its role in ischemic renal injury (IRI) is unknown. SIRT5 expression was increased in murine PTECs after IRI in vivo and in human PTECs (hPTECs) exposed to an oxygen/nutrient deprivation (OND) model of IRI in vitro. SIRT5-depletion impaired ATP production, reduced mitochondrial membrane potential, and provoked mitochondrial fragmentation in hPTECs. Moreover, SIRT5 RNAi exacerbated OND-induced mitochondrial bioenergetic dysfunction and swelling, and increased degradation by mitophagy. These findings suggest SIRT5 is required for normal mitochondrial function in hPTECs and indicate a potentially important role for the enzyme in the regulation of mitochondrial biology in ischemia.

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