Localization of C-X-C and C-C chemokines to renal tubular epithelial cells in human kidney transplants is not confined to acute cellular rejection

Abstract Introduction: The present study focuses on the interaction between long non-coding RNA GAS5 and microRNA-205-5p and their roles in cisplatin-induced acute kidney injury. Methods: Human kidney tubular cells (HK-2) were used to simulate acute renal injury induced by cisplatin with the consequent fluctuating expression levels of GAS5 and MIR-205-5p being determined respectively. Furthermore, the modulating effects of miR-205-5p and GAS5 in cisplatin-induced apoptosis of renal tubular epithelial cells and the possible binding sites between them were evaluated. Results: The results depicted that the expression of GAS5 was significantly up-regulated after AKI induced by cisplatin, while inhibiting the increase of expression would alleviate the apoptotic-promoting effect of cisplatin on renal tubular epithelial cells. MIR-205-5p is negatively regulated by GAS5, thus down-regulation of GAS5 will consequently elevate the expression of miR-205-5p and further alleviate the damage of HK-2 cells induced by cisplatin. Conclusions: In conclusion, in cisplatin-induced AKI, the expression of GAS5 was increased and consequently inhibited that of miR-205-5p by direct binding, which eventually aggravate the renal tubular epithelial injury, indicating their potential of being important diagnostic markers and therapeutic targets in the treatment of cisplatin-induced AKI.

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PM2.5 exposure induces renal injury via the activation of the autophagic pathway in rat and HK-2 cell

10.21203/rs.3.rs-23189/v1 ◽

2020 ◽

Author(s):

Xiaoliu Huang ◽

Jue Li

Keyword(s):

Epithelial Cells ◽

Renal Injury ◽

Fine Particulate Matter ◽

Human Kidney ◽

Kidney Damage ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Renal Tubular

Abstract Background Exposure to airborne fine particulate matter (PM2.5) has been declared to be harmful to the human kidney. However, whether activation of the autophagic pathway plays key roles in the nephrotoxicity caused by PM2.5 exposure is still poorly understood. The aim of this study was to explore the mechanism of kidney damage after PM2.5 exposure in vivo and in vitro. Results In the present study, statistically significant alterations in water intake, urine flow rate and mean blood pressure were observed between the PM2.5 group and FA group during the period of PM2.5 exposure. Exposed animals showed severe edema of renal tubular epithelial cells, capillary congestion, reduction of the glomerular urinary space and early pro-fibrotic state. Moreover, significant increases in the levels of early kidney damage markers were observed in the exposed rats and these animals exhibited more apoptosis rate in kidney cells. In addition, PM2.5 exposure resulted in the activation of the autophagic pathway, as evidenced by LC3-I to LC3-II conversion, P62 and beclin-1 activated. All of these effects are in concurrence with the presence of more autophagosomes both in vivo and in vitro after PM2.5 exposure. Conclusions Taken together, our findings indicated that PM2.5-induced renal injury via the activation of the autophagic pathway in renal tubular epithelial cells.

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PM2.5 exposure induced renal injury via the activation of the autophagic pathway in the rat and HK-2 cell

10.21203/rs.3.rs-23189/v2 ◽

2020 ◽

Author(s):

Xiaoliu Huang ◽

Zhitong Zhou ◽

Xinwen Liu ◽

Jue Li ◽

Lijuan Zhang

Keyword(s):

Epithelial Cells ◽

Fine Particulate Matter ◽

Human Kidney ◽

Kidney Damage ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Function Impairment ◽

Renal Tubular

Abstract Background: Exposure to airborne fine particulate matter (PM2.5) has been declared to be harmful to human kidney. However, whether activation of the autophagic pathway plays key roles in the nephrotoxicity caused by PM2.5 exposure is still poorly understood. The aim of this study was to explore the mechanism of kidney damage after PM2.5 exposure in vivo and in vitro.Results: In the present study, statistically significant alterations in water intake, urine flow rate and mean blood pressure were observed between the concentrated PM2.5 (PM2.5) group and the filtered air (FA) group. Exposed animals showed severe edema of renal tubular epithelial cells, capillary congestion, reduction of the glomerular urinary space and early pro-fibrotic state. Moreover, significant increases in the levels of early kidney damage markers were observed in the exposed rats and these animals exhibited more apoptosis rate in kidney cells. In addition, PM2.5 exposure activated the autophagic pathway, as evidenced by LC3-I to LC3-II conversion, activation of P62 and beclin-1. All of these effects are in concurrence with the presence of more autophagosomes both in vivo and in vitro after PM2.5 exposure. Conclusions: Taken together, our findings indicated that PM2.5-induced renal function impairment via the activation of the autophagic pathway in renal tubular epithelial cells.

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Influence of a bearing-wastewater phenolic compound (3,4-dimethylphenol, 3,4-DMP) treatment on Ca2+ homeostasis and its related cytotoxicity in human proximal renal tubular epithelial cells

Human & Experimental Toxicology ◽

10.1177/09603271211013453 ◽

2021 ◽

pp. 096032712110134

Author(s):

K-J Cheng ◽

W-Z Liang

Keyword(s):

Endoplasmic Reticulum ◽

Epithelial Cells ◽

Phenolic Compound ◽

Environmental Pollutants ◽

Human Kidney ◽

Industrial Effluents ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Cytotoxic Effects ◽

Renal Tubular

A lot of phenolic compounds are widespread in industrial effluents and they are considerable environmental pollutants. Being a compound commercially available, the effect of a bearing-wastewater phenolic compound 3,4-dimethylphenol (3,4-DMP) on Ca2+ homeostasis and its related physiology has not been explored in cultured human kidney cell models. The aim of this study was to explore the effect of 3,4-DMP on [Ca2+]i and viability in HK-2 human proximal renal tubular epithelial cells. In terms of Ca2+ signaling, 3,4-DMP (5–100 μM) induced [Ca2+]i rises only in HK-2 cells and Ca2+ removal reduced the signal by 40%. In Ca2+-containing medium, 3,4-DMP-induced Ca2+ entry was inhibited by 20% by a modulator of store-operated Ca2+ channels (2-APB), and by a PKC activator (PMA) and inhibitor (GF109203X). Moreover, 3,4-DMP-induced Mn2+ influx suggesting of Ca2+ entry. In Ca2+-free medium, inhibition of PLC with U73122 abolished 3,4-DMP-induced [Ca2+]i rises. Furthermore, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished 3,4-DMP-evoked [Ca2+]i rises. Conversely, treatment with 3,4-DMP abolished thapsigargin-evoked [Ca2+]i rises. Regarding to cell viability, 3,4-DMP (60–140 μM) killed cells in a concentration-dependent fashion in HK-2 cells. Chelation of cytosolic Ca2+ with BAPTA-AM partially reversed cytotoxicity of 3,4-DMP. Collectively, our data suggest that in HK-2 cells, 3,4-DMP-induced [Ca2+]i rises by evoking Ca2+ entry via PKC-sensitive store-operated Ca2+ entry and PLC-dependent Ca2+ release from the endoplasmic reticulum. 3,4-DMP also caused cytotoxicity that was linked to preceding [Ca2+]i rises. Our findings provide new insight into the cytotoxic effects of 3,4-DMP and the possible mechanisms underlying these effects.

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