Role of the Nox4/AMPK/mTOR signaling axe in adipose inflammation-induced kidney injury

Njeim, Rachel; Farhat, Theresa; Alkhansa, Sahar; Youssef, Natalie; Dia, Batoul; Slika, Rasha; Diab, Radwan; Azar, Sami T.; Eid, Assaad A.

doi:10.1042/cs20190584

Cited by 6 publications

(3 citation statements)

References 194 publications

(169 reference statements)

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“…As Nox4/AMPK/mTOR signaling has been reported to be implicated in diabetic kidney disease ( 21 ), we hypothesized that the AMPK/mTOR signaling might be implicated in Nox4-mediated regulation of HG-induced injury. HK-2 cells were transfected with si-Nox4 and treated with HG in combination with the AMPK activator AICAR or the mTOR activator propranolol.…”

Section: Resultsmentioning

confidence: 99%

“…Nox4 has been reported to be upregulated in high glucose-treated renal tubular epithelial cells, and it regulated high glucose-induced cell apoptosis through the Notch signaling ( 20 ). The Nox4/AMPK/mTOR signaling play important roles in diabetic renal disease ( 21 ). Puerarin ameliorated diabetic renal injury by inhibiting the expression of Nox4 in podocytes, indicating that Nox4 could be targeted for DN treatment.…”

Section: Introductionmentioning

confidence: 99%

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LncRNA MALAT1 Aggravates Renal Tubular Injury via Activating LIN28A and the Nox4/AMPK/mTOR Signaling Axis in Diabetic Nephropathy

et al. 2022

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BackgroundDiabetic nephropathy (DN) is a serious complication among patients with diabetes. Elucidating its pathogenesis is crucial for identifying novel biomarkers and therapeutic targets for DN.MethodsDN tissues were harvested for examining MALAT1, LIN28A and Nox4. Human kidney-2 (HK-2) cells were treated with high glucose (HG) for establishing a cell model of DN. Cell viability was examined by MTT assay. HG-induced cell apoptosis and secretion of TNF-α and IL-6 were analyzed by TUNEL and ELISA assays, respectively. RIP and RNA pull-down assays were applied to analyze the interaction between MALAT1, LIN28A and Nox4 in HK-2 and human embryonic kidney 293T (HEK-293T) cells. A rat model of DN was established to determine the role of MALAT1 in DN in vivo.ResultsMALAT1, LIN28A and Nox4 were upregulated in DN tissues and HG-treated HK-2 cells. Overexpression of MALAT1, LIN28A or Nox4 reduced cell viability and enhanced cell apoptosis, ROS generation and secretion of inflammatory cytokines in HG-treated HK-2 cells, whereas knockdown of MALAT1, LIN28A or Nox4 exerted opposite effects. Furthermore, MALAT1 directly interacted with LIN28A. Moreover, MALAT1 facilitated the interaction between LIN28A and Nox4 to increase Nox4 stability. Knockdown of Nox4 relieved HG-induced injury by suppressing the AMPK/mTOR signaling in HK-2 cells. Knockdown of MALAT1 alleviated renal tubular epithelial injury by suppressing LIN28A and the Nox4/AMPK/TOR signaling in DN.ConclusionMALAT1 activates the AMPK/mTOR signaling via interacting with LIN28A to stabilize Nox4 mRNA, thereby aggravating high glucose-induced renal tubular epithelial injury. Our findings provide potential therapeutic targets for DN.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LncRNA MALAT1 Aggravates Renal Tubular Injury via Activating LIN28A and the Nox4/AMPK/mTOR Signaling Axis in Diabetic Nephropathy

et al. 2022

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“…Increasing evidence has shown that CTSK could promote tumor cells proliferation via mTOR signaling pathway 32,33 . The mTOR signaling pathway, as a critical intracellular pathway, is involved in cell proliferation, growth, apoptosis, differentiation, in ammation, and survival 34,35 . p70S6K and 4EBP1 are key downstream substrates of mTOR1.…”

Section: Discussionmentioning

confidence: 99%

Cathepsin K promotes bone invasion of pituitary adenomas via interacting with TLR4 to mediate RANKL expression

Liu,

Wang,

Wang

et al. 2024

Preprint

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Purpose: This study aimed to explore the regulation and mechanism of Cathepsin K (CTSK) in bone invasive pituitary adenomas (BIPAs). Experimental Design: A total of 1437 patients with pituitary adenomas were included and followed up. RNA sequencing, immunohistochemistry, and RT-PCR were used to analyze to detect CTSK expression. The impact of CTSK on cellular proliferation, bone matrix degradation, and osteoclasts differentiation was determined by gain/loss of function experiments in vitro and vivo. The exploration of signaling pathway was determined by molecular biology experiments. Results: Here, we reported a significant fraction (~10%) of pituitary adenoma patients developed bone invasion. Bone invasion was correleted with tumor recurrence. Shorter recurrence free survival was found in BIPA patients. CTSK expression was increased in BIPA patients and strongly associated with worse prognosis. Increased CTSK expression promoted pituitary adenoma cell proliferation via activation of mammalian target of rapamycin (mTOR) signaling pathway and bone invasion via increasing osteoclast differentiation in vitro and in vivo. CTSK inhibitor (odanacatib) could inhibit pituitary adenoma cell proliferation and bone invasion in vitro and in vivo. CTSK promoted osteoclast differentiation by promoting the RANKL expression of MC3T3-E1 cells through interaction with TLR4. Conclusion: CTSK may become a novel predictive biomarker and potential therapeutic target for BIPAs.

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Dexmedetomidine Alleviates Acute Stress-Induced Acute Kidney Injury by Attenuating Inflammation and Oxidative Stress via Inhibiting the P2X7R/NF-κB/NLRP3 Pathway in Rats

Yang,

Zhao,

Chen

et al. 2024

Inflammation

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Role of the Nox4/AMPK/mTOR signaling axe in adipose inflammation-induced kidney injury

Cited by 6 publications

References 194 publications

LncRNA MALAT1 Aggravates Renal Tubular Injury via Activating LIN28A and the Nox4/AMPK/mTOR Signaling Axis in Diabetic Nephropathy

LncRNA MALAT1 Aggravates Renal Tubular Injury via Activating LIN28A and the Nox4/AMPK/mTOR Signaling Axis in Diabetic Nephropathy

Cathepsin K promotes bone invasion of pituitary adenomas via interacting with TLR4 to mediate RANKL expression

Dexmedetomidine Alleviates Acute Stress-Induced Acute Kidney Injury by Attenuating Inflammation and Oxidative Stress via Inhibiting the P2X7R/NF-κB/NLRP3 Pathway in Rats

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