Pyrroloquinoline quinone ameliorates renal fibrosis in diabetic nephropathy by inhibiting the pyroptosis pathway in C57BL/6 mice and human kidney 2 cells

XueFeng, Qu; Zhai, Bingzhong; Liu, Yifeng; Chen, Yi-Hao; Xie, Zemi; Wang, Qinxi; Wu, Yue-Jin; Liu, Zhen; Chen, Jianguo; Song, Moshi; Wu, Jie; You, Zhang; Yu, Yongjie; Wang, Yin

doi:10.1016/j.biopha.2022.112998

Cited by 27 publications

(13 citation statements)

References 23 publications

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“…14 A recent report shows that PQQ reduces renal fibrosis by improving mitochondrial function, reducing ROS production and inhibiting NF-κB/ pyroptosis signalling in diabetic nephropathy and hyperglycemia. 15 Our current investigation has revealed the effectiveness of PQQ in preventing pulmonary fibrosis that results from prolonged exposure to PM2.5. By inhibiting AEII cell migration when exposed to PM2.5, PQQ demonstrated its efficacy in targeting EMT as indicated by changes observed in cellular morphology and expression levels of EMT markers.…”

Section: Pqq Has Been Observedmentioning

confidence: 80%

“…PQQ was found to alleviate mitochondrial dysfunction, reduce ROS production and inhibit the activation of the NF-κB/pyroptosis pathway, leading to a potential therapeutic intervention for diabetic nephropathy and hyperglycemia-induced renal fibrosis. 15 However, the comprehensive investigation of the mechanism by which PQQ averts PM2.5-triggered pulmonary fibrosis via 23 which may occur inside the gastrointestinal tract during uptake. In the current study, we conducted intraperitoneal administration in the animals to evaluate the effects of PQQ engagement, focusing on its pharmacological and proof-of-concept aspects rather than on the properties of its pharmacokinetics for clinical translation.…”

Section: Discussionmentioning

confidence: 99%

“…A previous report has showed that PQQ plays a role in diverse biological processes linked to cognitive capabilities, immune reactivity and protection against ischemic occurrences affecting both the heart and nervous system 14 . A recent report shows that PQQ reduces renal fibrosis by improving mitochondrial function, reducing ROS production and inhibiting NF‐κB/pyroptosis signalling in diabetic nephropathy and hyperglycemia 15 …”

Section: Introductionmentioning

confidence: 99%

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Pyrroloquinoline quinone ameliorates PM2.5‐induced pulmonary fibrosis through targeting epithelial–mesenchymal transition

Chao,

Hsiao,

Kao

et al. 2024

J Cellular Molecular Medi

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Pulmonary fibrosis is a lung disorder affecting the lungs that involves the overexpressed extracellular matrix, scarring and stiffening of tissue. The repair of lung tissue after injury relies heavily on Type II alveolar epithelial cells (AEII), and repeated damage to these cells is a crucial factor in the development of pulmonary fibrosis. Studies have demonstrated that chronic exposure to PM2.5, a form of air pollution, leads to an increase in the incidence and severity of pulmonary fibrosis by stimulation of epithelial–mesenchymal transition (EMT) in lung epithelial cells. Pyrroloquinoline quinone (PQQ) is a bioactive compound found naturally that exhibits potent anti‐inflammatory and anti‐oxidative properties. The mechanism by which PQQ prevents pulmonary fibrosis caused by exposure to PM2.5 through EMT has not been thoroughly discussed until now. In the current study, we discovered that PQQ successfully prevented PM2.5‐induced pulmonary fibrosis by targeting EMT. The results indicated that PQQ was able to inhibit the expression of type I collagen, a well‐known fibrosis marker, in AEII cells subjected to long‐term PM2.5 exposure. We also found the alterations of cellular structure and EMT marker expression in AEII cells with PM2.5 incubation, which were reduced by PQQ treatment. Furthermore, prolonged exposure to PM2.5 considerably reduced cell migratory ability, but PQQ treatment helped in reducing it. In vivo animal experiments indicated that PQQ could reduce EMT markers and enhance pulmonary function. Overall, these results imply that PQQ might be useful in clinical settings to prevent pulmonary fibrosis.

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Section: Pqq Has Been Observedmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pyrroloquinoline quinone ameliorates PM2.5‐induced pulmonary fibrosis through targeting epithelial–mesenchymal transition

Chao,

Hsiao,

Kao

et al. 2024

J Cellular Molecular Medi

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“…The results showed that hydrogen peroxide (H2O2) and other free radicals were eliminated, accompanied by decreased expression of dynamin-related protein 1 (Drp1), caspase-1, and IL-1β, but whether GSDMD was cleaved in this process still needs further study. Moreover, Qu et al (2022) demonstrated that pyrroloquinoline quinone (PQQ) can reduce mitochondrial dysfunction and ROS production, and improved renal fibrosis induced by hyperglycemia. In addition, Gao et al (2022b) restored mitochondrial morphology by culturing podocytes with sialic acid precursor N-acetylmannosamine (ManNAc) and inhibited HG-induced pyroptosis by ROS/NLRP3 signaling pathway.…”

Section: Pyroptosis and Drugs In Diabetic Nephropathymentioning

confidence: 99%

NLRP3-mediated pyroptosis in diabetic nephropathy

Wan

Pan

et al. 2022

Front. Pharmacol.

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Diabetic nephropathy (DN) is the main cause of end-stage renal disease (ESRD), which is characterized by a series of abnormal changes such as glomerulosclerosis, podocyte loss, renal tubular atrophy and excessive deposition of extracellular matrix. Simultaneously, the occurrence of inflammatory reaction can promote the aggravation of DN-induced kidney injury. The most important processes in the canonical inflammasome pathway are inflammasome activation and membrane pore formation mediated by gasdermin family. Converging studies shows that pyroptosis can occur in renal intrinsic cells and participate in the development of DN, and its activation mechanism involves a variety of signaling pathways. Meanwhile, the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome can not only lead to the occurrence of inflammatory response, but also induce pyroptosis. In addition, a number of drugs targeting pyroptosis-associated proteins have been shown to have potential for treating DN. Consequently, the pathogenesis of pyroptosis and several possible activation pathways of NLRP3 inflammasome were reviewed, and the potential drugs used to treat pyroptosis in DN were summarized in this review. Although relevant studies are still not thorough and comprehensive, these findings still have certain reference value for the understanding, treatment and prognosis of DN.

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“…An increasing number of studies have shown that hyperglycemia, hypertension, obesity, and abnormal lipid metabolism all contribute to the occurrence and development of DN. Among them, the oxidative stress caused by high glucose is one of the main pathogenesis of DN. − Oxidative stress generates excess reactive oxygen species (ROS), which stimulates abnormal accumulation of extracellular matrix proteins in the kidney, thereby leading to renal glomerulosclerosis and tubulointerstitial fibrosis. , Meanwhile, high glucose promotes the synthesis of angiotensin II (Ang II), and the increase in Ang II level directly causes the constriction of blood vessels and the increase of glomerular pressure . The studies have shown that high glucose induces changes in the expression level of apoptosis-related proteins in HK-2 cells, which promotes cell apoptosis. − …”

Section: Introductionmentioning

confidence: 99%

Intestinal Absorption of Nanoparticles to Reduce Oxidative Stress and Vasoconstriction for Treating Diabetic Nephropathy

Liu,

Pang,

Wang

et al. 2024

ACS Biomater. Sci. Eng.

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The etiology of diabetic nephropathy (DN) is complex, and the incidence is increasing year by year. The patient's kidney showed oxidative stress damage, increasing active oxygen species (ROS) content, and vasoconstriction. Due to poor drug solubility and low renal accumulation, the current treatment regimens have not effectively alleviated glomerulopathy and other kidney damage caused by DN. Therefore, it is of great significance to explore new treatment strategies and drug delivery systems. Here, we constructed an oral nanodelivery system (Tel/CAN@CS-DA) that reduced oxidative stress and vasoconstriction. Deoxycholic acid (DA)-modified nanoparticles entered into intestinal epithelial cells (Caco2 cells) via the bile acid biomimetic pathway, then escaped from the lysosomes and eventually spat out the cells, increasing the oral absorption of nanoparticles. Chitosan (CS) nanoparticles could achieve renal targeting through specific binding with a renal giant protein receptor and deliver drugs to renal tubule epithelial cells (HK-2 cells). In vitro studies also proved that telmisartan (Tel) and canagliflozin (CAN) effectively removed cellular reactive oxygen species (ROS) and reduced HK-2 cell apoptosis caused by high glucose. In the in vivo model induced by streptozotocin (STZ), the results showed that the nanosystem not only elevated AMPK protein expression, inhibited angiotensin II (Ang II) protein expression to effectively reduce oxidative stress level, dilated renal blood vessels but also reduced the degree of inflammation and fibrosis. Overall, Tel/CAN@CS-DA multifunctional oral nanosystem can effectively treat DN with low toxicity, which provides a new idea for the treatment of DN.

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Pyrroloquinoline quinone ameliorates renal fibrosis in diabetic nephropathy by inhibiting the pyroptosis pathway in C57BL/6 mice and human kidney 2 cells

Cited by 27 publications

References 23 publications

Pyrroloquinoline quinone ameliorates PM2.5‐induced pulmonary fibrosis through targeting epithelial–mesenchymal transition

Pyrroloquinoline quinone ameliorates PM2.5‐induced pulmonary fibrosis through targeting epithelial–mesenchymal transition

NLRP3-mediated pyroptosis in diabetic nephropathy

Intestinal Absorption of Nanoparticles to Reduce Oxidative Stress and Vasoconstriction for Treating Diabetic Nephropathy

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