Advances in understanding the innate immune‐associated diabetic kidney disease

Wan, Shengfeng; Wan, Shengkai; Jiao, Xiaojing; Cao, Huixia; Gu, Yue; Liang, Yan; Zheng, Yan; Niu, Peiyuan; Shao, Fengmin

doi:10.1096/fj.202002334r

Cited by 14 publications

(16 citation statements)

References 136 publications

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“…The priming step is stimulated by the binding of pathogen-associated molecular patterns (PAMPs) and/or DAMPs to toll-like receptors and/or cytokine receptors. This step often involves the activation of NF-κB signaling and regulation of downstream genes that increase the expression of inflammasome-associated genes and substrates ( 10 , 21 ). Following priming, the activation step involves NLRP3 oligomerization and the assembly of inflammasome components into a complex.…”

Section: Immunomodulators Involved In Dn Pathogenesismentioning

confidence: 99%

“…This has severely hindered researchers to elucidate the role of immune system in progression of DN. Nevertheless, studies have been able to uncover a central role for immune-mediated inflammation in DN, involving both the innate and adaptive branches ( 7 , 8 , 10 – 12 ). Macrophages, as the predominant innate immune cells in DN, are commonly observed in the glomeruli and interstitium in experimental DN models and clinical trials at all stages of DN ( 13 – 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Immune responses in diabetic nephropathy: Pathogenic mechanisms and therapeutic target

Liu

2022

Front. Immunol.

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Diabetic nephropathy (DN) is a chronic, inflammatory disease affecting millions of diabetic patients worldwide. DN is associated with proteinuria and progressive slowing of glomerular filtration, which often leads to end-stage kidney diseases. Due to the complexity of this metabolic disorder and lack of clarity about its pathogenesis, it is often more difficult to diagnose and treat than other kidney diseases. Recent studies have highlighted that the immune system can inadvertently contribute to DN pathogenesis. Cells involved in innate and adaptive immune responses can target the kidney due to increased expression of immune-related localization factors. Immune cells then activate a pro-inflammatory response involving the release of autocrine and paracrine factors, which further amplify inflammation and damage the kidney. Consequently, strategies to treat DN by targeting the immune responses are currently under study. In light of the steady rise in DN incidence, this timely review summarizes the latest findings about the role of the immune system in the pathogenesis of DN and discusses promising preclinical and clinical therapies.

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Section: Immunomodulators Involved In Dn Pathogenesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune responses in diabetic nephropathy: Pathogenic mechanisms and therapeutic target

Liu

2022

Front. Immunol.

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“…Targeted Negative Regulation of JAK-STAT Signaling in Diabetic wound Specific Phases May Promote Healing JAK-STAT signaling includes four JAKs (JAK1, JAK2, JAK3, and Tyk2).and seven STATs (STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, AND STAT6). (Wan et al, 2021), and is essential for the maintenance of homeostasis. Elevated IFN-γ and JAK-STAT1 in obese patients induce adipocyte dysfunction and insulin resistance (McGillicuddy et al, 2009).…”

Section: Therapeutic Targeting Of Nlr Signaling In Diabetic Woundmentioning

confidence: 99%

Innate Immunity in Diabetic Wound Healing: Focus on the Mastermind Hidden in Chronic Inflammatory

Geng

Jiang³

et al. 2021

Front. Pharmacol.

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A growing body of evidence suggests that the interaction between immune and metabolic responses is essential for maintaining tissue and organ homeostasis. These interacting disorders contribute to the development of chronic diseases associated with immune-aging such as diabetes, obesity, atherosclerosis, and nonalcoholic fatty liver disease. In Diabetic wound (DW), innate immune cells respond to the Pathogen-associated molecular patterns (PAMAs) and/or Damage-associated molecular patterns (DAMPs), changes from resting to an active phenotype, and play an important role in the triggering and maintenance of inflammation. Furthermore, the abnormal activation of innate immune pathways secondary to immune-aging also plays a key role in DW healing. Here, we review studies of innate immune cellular molecular events that identify metabolic disorders in the local microenvironment of DW and provide a historical perspective. At the same time, we describe some of the recent progress, such as TLR receptor-mediated intracellular signaling pathways that lead to the activation of NF-κB and the production of various pro-inflammatory mediators, NLRP3 inflammatory via pyroptosis, induction of IL-1β and IL-18, cGAS-STING responds to mitochondrial injury and endoplasmic reticulum stress, links sensing of metabolic stress to activation of pro-inflammatory cascades. Besides, JAK-STAT is also involved in DW healing by mediating the action of various innate immune effectors. Finally, we discuss the great potential of targeting these innate immune pathways and reprogramming innate immune cell phenotypes in DW therapy.

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“…Glomerular mesangial cells (MCs) are major components of the glomerular mesangium, hold the capillary arteries and connect them with the juxtaglomerular apparatus. More and more evidences are suggesting the abnormal growth of MCs is an early event in various glomerular diseases ( Yoon et al, 2020 ; Wan et al, 2021 ). Targeting glomerular mesangial cells as the research object and screening for suitable drugs to repair the damage caused by oxidative stress and inflammation have important scientific research significance and clinical value.…”

Section: Protective Effect Of Panax Ginseng Camey On Renal Innate Cellsmentioning

confidence: 99%

Panax Ginseng C.A.Mey. as Medicine: The Potential Use of Panax Ginseng C.A.Mey. as a Remedy for Kidney Protection from a Pharmacological Perspective

Jin

Zhang

et al. 2021

Front. Pharmacol.

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Panax ginseng C.A.Mey. has been widely consumed as food/diet supplements from natural sources, and its therapeutic properties have also aroused widespread concern. Therapeutic properties of Panax ginseng C.A.Mey. such as anti-inflammatory, ameliorating chronic inflammation, enhancing the immunity, resisting the oxidation again, and regulating the glucose and lipid metabolism have been widely reported. Recent years, lots of interesting studies have reported the potential use of Panax ginseng C.A.Mey. in the management of DKD. DKD has become the leading cause of end-stage renal disease worldwide, which increases the risk of premature death and poses a serious financial burden. Although DKD is somehow controllable with different drugs such as Angiotensin-Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARB) and lowering-glucose agents, modern dietary changes associated with DKD have facilitated research to assess the preventive and therapeutic merits of diet supplements from natural sources as medicine including Panax ginseng C.A.Mey. Findings from many scientific evidences have suggested that Panax ginseng C.A.Mey. can relieve the pathological status in cellular and animal models of DKD. Moreover, a few studies showed that alleviation of clinical phenotype such as reducing albuminuria, serum creatinine and renal anemia in DKD patients after application or consumption of Panax ginseng C.A.Mey.. Therefore, this review aims to discuss the effectiveness of Panax ginseng C.A.Mey. as medicine for targeting pathological phenotypes in DKD from a pharmacological perspective. This review will provide new insights into the potential understanding use of Panax ginseng C.A.Mey. in the management of DKD in clinical settings.

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Advances in understanding the innate immune‐associated diabetic kidney disease

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 14 publications

References 136 publications

Immune responses in diabetic nephropathy: Pathogenic mechanisms and therapeutic target

Immune responses in diabetic nephropathy: Pathogenic mechanisms and therapeutic target

Innate Immunity in Diabetic Wound Healing: Focus on the Mastermind Hidden in Chronic Inflammatory

Panax Ginseng C.A.Mey. as Medicine: The Potential Use of Panax Ginseng C.A.Mey. as a Remedy for Kidney Protection from a Pharmacological Perspective

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