Pro-resolving lipid mediators: regulators of inflammation, metabolism and kidney function

Brennan, Eoin; Kantharidis, Phillip; Cooper, Mark E.; Godson, Catherine

doi:10.1038/s41581-021-00454-y

Cited by 131 publications

(74 citation statements)

References 202 publications

(242 reference statements)

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“…Numerous hard-to-treat disorders, including cardiovascular disease, diabetes, and neurological issues, have been intimately connected with uncontrolled inflammation [ 32 ]. Emerging evidence suggests the pivotal role of specific lipid mediators in modulating inflammation resolution [ 33 ]. The present study showed that the DHA products RvD1 and PD1 reduce CaOx deposition by alleviating the ROS-induced inflammatory response, providing strong evidence for the inhibitory effect of active lipid components on inflammation and expanding our understanding of the role of lipid components in inflammation regulation.…”

Section: Discussionmentioning

confidence: 99%

Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones

Wang

Wei

Huangfu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Intrarenal calcium oxalate (CaOx) crystals induce renal tubular epithelial cell (TEC) inflammatory and oxidative injury. This study is aimed at exploring potential therapeutic lipid components in kidney stones because lipids are involved in the development of several diseases and indicate the risk of kidney stones. Serum specimens were collected from 35 kidney stone patients and 35 normal controls. The lipid components in serum were measured, and differences were analyzed. The documented biological importance was comprehensively reviewed to identify lipids that differed significantly between the two groups to find potential agents associated with kidney stones. CaOx nephrocalcinosis mouse model was established to examine the therapeutic effects of specific lipids on CaOx deposition and CaOx-induced oxidative renal injury. Several lipids with significantly different levels were present in the serum of patients with stones and normal controls. Resolvin D1 (RvD1) (4.93-fold change, P < 0.001 ) and protectin D1 (PD1) (5.06-fold change, P < 0.001 ) were significantly decreased in the serum of patients with kidney stones, and an integrative review suggested that these factors might be associated with inflammatory responses, which is a crucial mechanism associated with stone damage. The administration of RvD1 and PD1 significantly inhibited kidney CaOx deposition and suppressed CaOx-induced renal tubular cell inflammatory injury and necrosis in a CaOx nephrocalcinosis mouse model. Furthermore, RvD1 and PD1 facilitated the expression of the oxidative indicator superoxide dismutase 2 (SOD2), inhibited NADPH oxidase 2 (NOX2) expression, and diminished intracellular reactive oxygen species (ROS) levels. This study preliminarily elucidated the role of lipids in kidney stones. The inhibitory effects of RvD1 and PD1 on oxidative damage induced by CaOx deposition provide a promising perspective for kidney stone treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones

Wang

Wei

Huangfu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“… 36 Obesity, diabetes mellitus, hypertension, and cardiovascular disease are believed to be among the underlying conditions that give rise to the low‐grade inflammation that impairs insulin signaling. 37 Several studies have also noted an association between CKD‐induced insulin resistance and muscle protein wasting. 4 , 38 Protein degradation is increased with CKD‐associated insulin resistance, and therefore, it is difficult to manage protein intake in these patients, especially those on a low‐protein diet.…”

Section: Discussionmentioning

confidence: 99%

TLR13 contributes to skeletal muscle atrophy by increasing insulin resistance in chronic kidney disease

Wang

Zhang

et al. 2022

Cell Proliferation

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Objectives Insulin resistance in chronic kidney disease (CKD) stimulates muscle wasting, but the molecular processes behind the resistance are undetermined. However, inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia. Toll‐like receptors (TLRs) are known to regulate local innate immune responses, and microarray data have shown that Tlr13 is upregulated in the muscles of mice with CKD, but the relevance is unknown. Materials and Methods We performed in vitro experiments in C2C12 myotubes and constructed a CKD murine model using subtotal nephrectomy to conduct experiments in vivo. Results Tlr13 expression was stimulated in C2C12 myotubes treated with uremic serum. The expression of Tlr13 was also upregulated in the tibialis anterior muscles of mice with CKD. Tlr13 knockdown with siRNAs in skeletal muscle cells decreased insulin resistance despite the inclusion of uremic serum. This led to increased levels of p‐AKT and suppression of protein degradation. Using immunofluorescence staining and coimmunoprecipitation assay, we found that TLR13 recruits IRF3, which activates Irf3 expression, resulting in decreased AKT activity. Moreover, insulin resistance and proteolysis are re‐induced by Irf3 overexpression under Tlr13 deletion. Conclusions Our results indicate that TLR13 is involved in CKD‐mediated insulin resistance in muscle. In catabolic conditions where insulin signaling is impaired, targeting TLR13 may improve insulin sensitivity and prevent muscle atrophy.

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“…A recent clinical trial reported that local topical treatment of gingival inflammation with a proresolving lipoxin/resolvin stable analog is safe and effective as well as activated endogenous production of SPMs present in peripheral blood [ 63 ]. A new generation of lipoxin stable analog mimetics introduced by investigators in Dublin hold exceptional promise for novel pro-resolving treatments in inflammation-resolution for kidney diseases and the many diabetic complications [ [64] , [65] , [66] ]. They demonstrated with analyses of nasal lavages that SPMs, e.g., RvD2, are dysregulated in human rhinosinusitis.…”

Section: Spms In Covid-19 Infections and Other Human Studiesmentioning

confidence: 99%

E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition

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Serhan

Libreros

et al. 2022

Seminars in Immunology

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Pro-resolving lipid mediators: regulators of inflammation, metabolism and kidney function

Abstract: An inflammatory response arising in the absence of a pathogen (for example, toxin exposure, mechanical tissue injury and ischaemia).

Cited by 131 publications

References 202 publications

Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones

Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones

TLR13 contributes to skeletal muscle atrophy by increasing insulin resistance in chronic kidney disease

E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition

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