Renal Tubular TRPA1 as a Risk Factor for Recovery of Renal Function from Acute Tubular Necrosis

Wu, Chung-Kuan; Wu, Ching-Kuan; Su, Tzu Cheng; Kou, Yu Ru; Kor, Chew Teng; Lee, Tzong‐Shyuan; Tarng, Der‐Cherng

doi:10.3390/jcm8122187

Cited by 13 publications

(13 citation statements)

References 30 publications

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“…CKF including renal tubular cell damage and death is the most common cause of CKD in hospitalized patients. 39,40 Studies using rat models of CKF have shown that adenine hemisulfate solution significantly increases BUN, serum creatinine, glomerular damage, tubular necrosis, interstitial fibrosis, and inflammatory mediators. 35,41,42 In addition, many inflammatory markers such as IL-1b, IL-6, IL-18, IL-33, and TNF-a increase during the progression of CKF.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin

Yazgan

Avcı

Memi

et al. 2021

Exp Biol Med (Maywood)

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Chronic kidney disease is a major global public health problem. The peptide hormones adropin and spexin modulate many physiological functions such as energy balance and glucose, lipid and protein metabolism. However, it is unclear whether these peptides may exert effects on renal damage, tissue remodeling, and inflammatory conditions. In view of the limited information, we aimed to investigate the effect of adropin and spexin on matrix metalloproteinase and inflammatory response genes a rat model of adenine-induced chronic kidney failure. Chronic kidney failure was induced in rats by administering adenine hemisulfate. Renal function was determined in an autoanalyzer. Histopathological modifications were assessed by H&E staining. mRNA expression levels of ALOX 15, COX 1, COX 2, IL-1β, IL-10, IL-17A, IL-18 IL-21, IL-33, KIM-1, MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, NGAL, TGFβ1, TIMP-1, and TNFα in kidney tissue were measured by qPCR. Our results showed an increase of 24-h urine volume, serum creatinine, BUN, and urine protein levels in group with adenine-induced CKF. Adropin and spexin treatments decreased urine protein and 24-h urine volume. Renal damage, TIMP-1, IL-33, and MMP-2 increased after CKF induction, while COX 1, MMP-9, and MMP-13 levels were significantly reduced. Furthermore, KIM-1, TIMP-1, IL-33, and MMP-2 were downregulated by spexin treatment. Renal damage, NGAL, TIMP-1 IL-17A, IL-33, MMP-2, and MMP-3 decreased after adropin treatment, while MMP-13 levels were upregulated. Treatment with adropin+spexin decreased KIM-1, NGAL, TIMP-1, IL-1β, IL-17A, IL-18, IL-33, ALOX 15, COX 1, COX 2, TGFβ1, TNFα, MMP-2, MMP-3, and MMP-7, but increased MMP-13 levels. Our findings revealed that inflammatory response and MMP genes were modulated by adropin and spexin. These peptides may have protective effects on inflammation and chronic kidney damage progression.

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Section: Discussionmentioning

confidence: 99%

Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin

Yazgan

Avcı

Memi

et al. 2021

Exp Biol Med (Maywood)

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“…In whole animals/humans, the role of TRPA1 in kidney disease remains unresolved. In a retrospective study, TRPA1 was upregulated in the renal tubules of patients with acute tubular necrosis and independently associated with failure to recover renal function 63 . Renal ischemia‐reperfusion injury (IRI) increased tubular TRPA1 expression in mice 64 .…”

Section: Discussionmentioning

confidence: 99%

Interleukin 1 beta‐induced calcium signaling via TRPA1 channels promotes mitogen‐activated protein kinase‐dependent mesangial cell proliferation

et al. 2021

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Glomerular mesangial cell (GMC)‐derived pleiotropic cytokine, interleukin‐1 (IL‐1), contributes to hypercellularity in human and experimental proliferative glomerulonephritis. IL‐1 promotes mesangial proliferation and may stimulate extracellular matrix accumulation, mechanisms of which are unclear. The present study shows that the beta isoform of IL‐1 (IL‐1β) is a potent inducer of IL‐1 type I receptor‐dependent Ca2+ entry in mouse GMCs. We also demonstrate that the transient receptor potential ankyrin 1 (TRPA1) is an intracellular store‐independent diacylglycerol‐sensitive Ca2+ channel in the cells. IL‐1β‐induced Ca2+ and Ba2+ influxes in the cells were negated by pharmacological inhibition and siRNA‐mediated knockdown of TRPA1 channels. IL‐1β did not stimulate fibronectin production in cultured mouse GMCs and glomerular explants but promoted Ca2+‐dependent cell proliferation. IL‐1β also stimulated TRPA1‐dependent ERK mitogen‐activated protein kinase (MAPK) phosphorylation in the cells. Concomitantly, IL‐1β‐induced GMC proliferation was attenuated by TRPA1 and RAF1/ MEK/ERK inhibitors. These findings suggest that IL‐1β‐induced Ca2+ entry via TRPA1 channels engenders MAPK‐dependent mesangial cell proliferation. Hence, TRPA1‐mediated Ca2+ signaling could be of pathological significance in proliferative glomerulonephritis.

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“…Despite advances in the management of CKD, this syndrome continues to be associated with unacceptable levels of morbidity and mortality [ 125 ]. A clinical observational study revealed that TRPA1 is upregulated in the renal tubules of patients with acute kidney injury (AKI) [ 126 ], leading study authors to suggest that TRPA1 is associated with the progression of AKI to CKD. Methylglyoxal, a reactive glucose metabolite, is elevated in CKD [ 127 ] and may be a central contributor to the inflammatory, structural, metabolic, and hemodynamic pathology of CKD [ 128 ].…”

Section: Trpa1 Channels and Vascular Diseasementioning

confidence: 99%

Transient Receptor Potential Channel Ankyrin 1: A Unique Regulator of Vascular Function

Alvarado

Thakore

Earley

2021

Cells

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TRPA1 (transient receptor potential ankyrin 1), the lone member of the mammalian ankyrin TRP subfamily, is a Ca2+-permeable, non-selective cation channel. TRPA1 channels are localized to the plasma membranes of various cells types, including sensory neurons and vascular endothelial cells. The channel is endogenously activated by byproducts of reactive oxygen species, such as 4-hydroxy-2-noneal, as well as aromatic, dietary molecules including allyl isothiocyanate, a derivative of mustard oil. Several studies have implicated TRPA1 as a regulator of vascular tone that acts through distinct mechanisms. First, TRPA1 on adventitial sensory nerve fibers mediates neurogenic vasodilation by stimulating the release of the vasodilator, calcitonin gene-related peptide. Second, TRPA1 is expressed in the endothelium of the cerebral vasculature, but not in other vascular beds, and its activation results in localized Ca2+ signals that drive endothelium-dependent vasodilation. Finally, TRPA1 is functionally present on brain capillary endothelial cells, where its activation orchestrates a unique biphasic propagation mechanism that dilates upstream arterioles. This response is vital for neurovascular coupling and functional hyperemia in the brain. This review provides a brief overview of the biophysical and pharmacological properties of TRPA1 and discusses the importance of the channel in vascular control and pathophysiology.

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Renal Tubular TRPA1 as a Risk Factor for Recovery of Renal Function from Acute Tubular Necrosis

Cited by 13 publications

References 30 publications

Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin

Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin

Interleukin 1 beta‐induced calcium signaling via TRPA1 channels promotes mitogen‐activated protein kinase‐dependent mesangial cell proliferation

Transient Receptor Potential Channel Ankyrin 1: A Unique Regulator of Vascular Function

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