Cytokine cooperation in renal tubular cell injury: The role of TWEAK

Abstract Hyperglycemia-induced renal tubular cell injury is thought to play a critical role in the pathogenesis of diabetic nephropathy (DN). However, the role of miRNAs in renal tubular cell injury remains to be fully elucidated. The aim of the present study was to investigate the role and mechanisms of miRNAs protecting against high glucose (HG)-induced apoptosis and inflammation in renal tubular cells. First, we analyzed microRNA (miRNA) expression profiles in kidney tissues from DN patients using miRNA microarray. It was observed that miRNA-140-5p (miR-140-5p) was significantly down-regulated in kidney tissues from patients with DN. An inverse correlation between miR-140-5p expression levels with serum proteinuria was observed in DN patients, suggesting miR-140-5p may be involved in the progression of DN. HG-induced injury in HK-2 cells was used to explore the potential role of miR-140-5p in DN. We found that miR-140-5p overexpression improved HG-induced cell injury, as evidenced by the enhancement of cell viability, and inhibition of the activity of caspase-3 and reactive oxygen species (ROS) generation. It was also observed that up-regulation of miR-140-5p suppressed HG induced the expressions of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in HK-2 cells. In addition, TLR4, one of the upstream molecules of NF-κB signaling pathway, was found to be a direct target of miR-140-5p in the HK-2. Moreover, the HG-induced activation of NF-κB signaling pathway was inhibited by miR-140-5p overexpression. These results indicated that miR-140-5p protected HK-2 cells against HG-induced injury through blocking the TLR4/NF-κB pathway, and miR-140-5p may be considered as a potential prognostic biomarker and therapeutic target in the treatment of DN.

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Role of intracellular calcium in hydrogen peroxide-induced renal tubular cell injury

AJP Renal Physiology ◽

10.1152/ajprenal.1992.263.2.f214 ◽

1992 ◽

Vol 263 (2) ◽

pp. F214-F221 ◽

Cited By ~ 6

Author(s):

N. Ueda ◽

S. V. Shah

Keyword(s):

Trypan Blue ◽

Cell Injury ◽

Tubular Cell ◽

Renal Tubular Cell ◽

Reactive Oxygen Metabolites ◽

Acetoxymethyl Ester ◽

Trypan Blue Exclusion ◽

Renal Tubular Cells ◽

Renal Tubular

Both reactive oxygen metabolites and calcium have been implicated in ischemic and toxic renal tubular cell injury. However, the role of calcium in oxidant injury to renal tubular cells has not been previously examined. In the present study we examined the role of intracellular free Ca2+ ([Ca2+]i) in H2O2-mediated injury to LLC-PK1 cells, a renal tubular epithelial cell line. H2O2 induced a significant rise in [Ca2+]i within 1 min after exposure of cells to 5 mM H2O2, with a sustained rise in [Ca2+]i during the course of experiments, reaching a value of 1.3 microM at 60 min (n = 10). The rise in [Ca2+]i preceded sublethal cell injury as measured by [3H]adenine release or irreversible cell injury as determined by trypan blue exclusion. Buffering [Ca2+]i with quin-2 (50 microM) and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA, 50 microM) was highly protective against the H2O2-induced cell injury. For example, at 120 min after exposure of cells to 5 mM H2O2, irreversible cell injury was reduced from 45 +/- 8 to 9 +/- 1% (n = 3) by quin-2. The acetoxymethyl ester of quin-2 (quin-2/AM) and BAPTA/AM did not interfere with the trypan blue exclusion assay or scavenge H2O2. Preventing mobilization of Ca2+ from intracellular storage sites using 8-(N,N-dimethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8, 10(-4) M) significantly reduced the rise in [Ca2+]i and thus prevented H2O2-mediated cytotoxicity to LLC-PK1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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The Role of Cell Calcium Overload in Nephrotoxic Renal Tubular Cell Injury

American Journal of Kidney Diseases ◽

10.1016/s0272-6386(86)80099-3 ◽

1986 ◽

Vol 8 (5) ◽

pp. 284-291 ◽

Cited By ~ 16

Author(s):

Joel M. Weinberg

Keyword(s):

Cell Injury ◽

Calcium Overload ◽

Tubular Cell ◽

Renal Tubular Cell ◽

Cell Calcium ◽

Renal Tubular

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Propylene glycol-induced proximal renal tubular cell injury

American Journal of Kidney Diseases ◽

10.1016/s0272-6386(97)90577-1 ◽

1997 ◽

Vol 30 (1) ◽

pp. 134-139 ◽

Cited By ~ 34

Author(s):

Peter D. Yorgin ◽

Andreas A. Theodorou ◽

Amira Al-Uzri ◽

Karen Davenport ◽

Leslie V. Boyer-Hassen ◽

...

Keyword(s):

Propylene Glycol ◽

Cell Injury ◽

Tubular Cell ◽

Renal Tubular Cell ◽

Renal Tubular

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HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells

AJP Renal Physiology ◽

10.1152/ajprenal.00178.2017 ◽

2017 ◽

Vol 313 (4) ◽

pp. F906-F913 ◽

Cited By ~ 37

Author(s):

Wei Zhang ◽

Xiangjun Zhou ◽

Qisheng Yao ◽

Yutao Liu ◽

Hao Zhang ◽

...

Keyword(s):

Cell Injury ◽

Hypoxia Inducible Factor ◽

Atp Depletion ◽

Tubular Cell ◽

Renal Tubular Cell ◽

Dependent Manner ◽

Protective Effects ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular

Exosomes are nano-sized vesicles produced and secreted by cells to mediate intercellular communication. The production and function of exosomes in kidney tissues and cells remain largely unclear. Hypoxia is a common pathophysiological condition in kidneys. This study was designed to characterize exosome production during hypoxia of rat renal proximal tubular cells (RPTCs), investigate the regulation by hypoxia-inducible factor-1 (HIF-1), and determine the effect of the exosomes on ATP-depletion-induced tubular cell injury. Hypoxia did not change the average sizes of exosomes secreted by RPTCs, but it significantly increased exosome production in a time-dependent manner. HIF-1 induction with dimethyloxalylglycine also promoted exosome secretion, whereas pharmacological and genetic suppression of HIF-1 abrogated the increase of exosome secretion under hypoxia. The exosomes from hypoxic RPTCs had inhibitory effects on apoptosis of RPTCs following ATP depletion. The protective effects were lost in the exosomes from HIF-1α knockdown cells. It is concluded that hypoxia stimulates exosome production and secretion in renal tubular cells. The exosomes from hypoxic cells are protective against renal tubular cell injury. HIF-1 mediates exosome production during hypoxia and contributes to the cytoprotective effect of the exosomes.

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