The role of cannabinoid signaling in acute and chronic kidney diseases

Barutta, Federica; Bruno, Graziella; Mastrocola, Raffaella; Bellini, Stefania; Gruden, Gabriella

doi:10.1016/j.kint.2018.01.024

Cited by 54 publications

(49 citation statements)

References 42 publications

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“…Notably, CB1R blockade also reversed changes in both albuminuria and renal function in animals with established albuminuria [43,45]. Mechanistically, modulation of the ECS appears to prevent albuminuria by preventing nephrin loss and podocyte apoptosis, while the beneficial effect on renal fibrosis is likely due reduced release of prosclerotic and pro-inflammatory factors [46].…”

Section: The Endocannabinod Systemmentioning

confidence: 91%

“…These compounds are currently under early stage clinical development with the aim of providing proof of safety and tolerability, including CNS safety. Moreover, compounds that are both CB1R antagonists and CB2R agonists may provide additional therapeutic benefits [46]. However, CB1R and CB2R can form heterodimers and their signalling pathways are deeply intertwined; therefore, further research is required to better elucidate their relationship and combined effects in order to avoid undesirable and/or off-target effects.…”

Section: The Endocannabinod Systemmentioning

confidence: 99%

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The future of diabetic kidney disease management: what to expect from the experimental studies?

et al. 2020

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Diabetic kidney disease (DKD) is a major cause of end-stage renal disease. Intensive blood glucose and blood pressure control, particularly using inhibitors of the renin-angiotensin system, have long been mainstays of therapy in patients with DKD. Moreover, new anti-hyperglycemic drugs have recently shown renoprotective effects and this represents a major progress in the management of DKD. However, the risk of progression is still substantial and additional drugs are required. Recent preclinical studies have identified novel therapeutic targets that may optimize renoprotection in the near future. Besides strategies aimed to reduce oxidative stress and inflammation in the kidney, novel extra-renal approaches targeting stem cells, extracellular vesicles, and the microbiota are on the horizon with promising preclinical data. Herein, we will review these lines of research and discuss potential clinical applications. Given the poor yield of experimental studies in DKD in the past years, we will also discuss strategies to improve translation of preclinical research to humans.

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Section: The Endocannabinod Systemmentioning

confidence: 91%

Section: The Endocannabinod Systemmentioning

confidence: 99%

The future of diabetic kidney disease management: what to expect from the experimental studies?

et al. 2020

Self Cite

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“…Great attention has recently been paid to the endocannabinoid system and related NAEs in the regulation of urinary tract homeostasis [161][162][163]. In the kidney, PEA is physiologically present from the embryonic stage [91,164] and is naturally produced in healthy and disease conditions [165,166].…”

Section: Upper and Lower Urinary Tractmentioning

confidence: 99%

Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing

Gugliandolo

Peritore

Piras

et al. 2020

Veterinary Sciences

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Virtually every cellular process is affected by diet and this represents the foundation of dietary management to a variety of small animal disorders. Special attention is currently being paid to a family of naturally occurring lipid amides acting through the so-called autacoid local injury antagonism, i.e., the ALIA mechanism. The parent molecule of ALIAmides, palmitoyl ethanolamide (PEA), has being known since the 1950s as a nutritional factor with protective properties. Since then, PEA has been isolated from a variety of plant and animal food sources and its proresolving function in the mammalian body has been increasingly investigated. The discovery of the close interconnection between ALIAmides and the endocannabinoid system has greatly stimulated research efforts in this field. The multitarget and highly redundant mechanisms through which PEA exerts prohomeostatic functions fully breaks with the classical pharmacology view of “one drug, one target, one disease”, opening a new era in the management of animals’ health, i.e., an according-to-nature biomodulation of body responses to different stimuli and injury. The present review focuses on the direct and indirect endocannabinoid receptor agonism by PEA and its analogues and also targets the main findings from experimental and clinical studies on ALIAmides in animal health and wellbeing.

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“…In contrary, recent data indicate that the activation of cannabinoid receptors dose-dependently decreases interleukin-6 (IL-6) and monocyte chemoattractant protein-1, as well as fibronectin, collagen 1, and α-smooth muscle actin levels in pancreatic stellate cells [8]. There are also contradictory results concerning the effects of cannabinoid receptors on renal tubulointerstitial fibrotic damage [11,12,13,14]. Targeted inhibition of CB1R or CB2R effectively reduces fibrosis in the kidneys of mice with unilateral ureteral obstruction [11,13].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-29a Attenuates Diabetic Glomerular Injury through Modulating Cannabinoid Receptor 1 Signaling

Tung

Hsu

et al. 2019

Molecules

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Diabetic nephropathy often leads to end-stage renal disease and life-threatening morbidities. Simple control of risk factors is insufficient to prevent the progression of diabetic nephropathy, hence the need for discovering new treatments is of paramount importance. Recently, the dysregulation of microRNAs or the cannabinoid signaling pathway has been implicated in the pathogenesis of various renal tubulointerstitial fibrotic damages and thus novel therapeutic targets for chronic kidney diseases have emerged; however, the role of microRNAs or cannabinoid receptors on diabetes-induced glomerular injuries remains to be elucidated. In high-glucose-stressed renal mesangial cells, transfection of a miR-29a precursor sufficiently suppressed the mRNA and protein expressions of cannabinoid type 1 receptor (CB1R). Our data also revealed upregulated CB1R, interleukin-1β, interleukin-6, tumor necrosis factor-α, c-Jun, and type 4 collagen in the glomeruli of streptozotocin (STZ)-induced diabetic mice, whereas the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) was decreased. Importantly, using gain-of-function transgenic mice, we demonstrated that miR-29a acts as a negative regulator of CB1R, blocks the expressions of these proinflammatory and profibrogenic mediators, and attenuates renal hypertrophy. We also showed that overexpression of miR-29a restored PPAR-γ signaling in the renal glomeruli of diabetic animals. Collectively, our findings indicate that the interaction between miR-29a, CB1R, and PPAR-γ may play an important role in protecting diabetic renal glomeruli from fibrotic injuries.

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The role of cannabinoid signaling in acute and chronic kidney diseases

Cited by 54 publications

References 42 publications

The future of diabetic kidney disease management: what to expect from the experimental studies?

The future of diabetic kidney disease management: what to expect from the experimental studies?

Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing

MicroRNA-29a Attenuates Diabetic Glomerular Injury through Modulating Cannabinoid Receptor 1 Signaling

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