The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease

Huang, Chunling; Bian, Ji; Cao, Qinghua; Chen, Xinming; Pollock, Carol

doi:10.3390/ijms22041525

Cited by 10 publications

(7 citation statements)

References 86 publications

(104 reference statements)

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“…The mechanisms involved have not been generally well studied except for PINK1-mediated mitophagy which plays a protective role in diabetic kidney disease ( Wang et al, 2021 ). Moreover, activating the PINK1-Parkin pathway has been suggested as a beneficial approach to restore mitophagy ( Huang et al, 2021 ). Our description of the regulatory mechanism involving FUNDC1-mediated mitophagy in models of type 2 diabetes offers new perspectives on the pathogenesis of DN.…”

Section: Discussionmentioning

confidence: 99%

Src Activation Aggravates Podocyte Injury in Diabetic Nephropathy via Suppression of FUNDC1-Mediated Mitophagy

et al. 2022

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Background and purpose: Mitophagy plays a significant role in the progression of diabetic nephropathy (DN), although the regulatory mechanisms remain unclear. Recently, accumulating evidence demonstrated that impaired mitochondrial function and mitophagy are involved in DN. Here, we are aimed to explore the role of c-Src (Src) and FUNDC1-related mitophagy in the development of DN.Methods: The db/db mice were used to establish a DN mice model. The mice accepted PP2 (Src inhibitor) treatment to study the role of Src in DN. Kidney function was measured via biochemical testing. Renal histopathology and morphometric analysis were conducted via hematoxylin-eosin (HE), periodic acid-Schiff (PAS), Masson’s staining, and transmission electron microscopy (TEM). We measured degree of apoptosis in kidney by TUNEL assay. Indices of mitophagy (LC3 and p62) were evaluated by Western blotting and immunofluorescence. Complementary in vitro assays were conducted using human podocytes subjected to high glucose in combination with PP2 treatment or FUNDC1 small interfering RNAs (siRNAs). Flow cytometry was used to detect the apoptotic cells. Mitochondrial function was evaluated by JC-1 staining. Double immunofluorescence labeling of LC3 and TOMM20 used to assess the degree of mitophagy.Results: Increased Src activation was detected in the kidneys of db/db mice, and its expression was positively correlated with mitochondrial damage, podocyte apoptosis, and renal dysfunction. Inhibition of Src activation with PP2 protected against mitochondrial damage and podocyte apoptosis. In vitro experiments in podocytes established that high glucose increased Src activation, promoting FUNDC1 phosphorylation and inhibiting mitophagy. Consistent with the mouse model, inhibiting Src activity protected podocytes against mitochondrial damage. FUNDC1 silencing negated the actions of PP2, indicating that FUNDC1-mediated mitophagy is downstream pathway of Src.Conclusion: In summary, our data indicated that Src is a culprit factor in diabetic renal damage via suppression of FUNDC1-mediated mitophagy, promoting the development of DN.

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Section: Discussionmentioning

confidence: 99%

Src Activation Aggravates Podocyte Injury in Diabetic Nephropathy via Suppression of FUNDC1-Mediated Mitophagy

et al. 2022

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“…CXCL10 [76], SIGLEC1 [77] and IL1R2 [78] have been suggested to be associated with neurological diseases. CXCL9 [79], SIGLEC1 [80], IL1R2 [81], KLF15 [82] and CD207 [83] [146], STAT4 [147], CXCL8 [148], KLF2 [149], ADM (adrenomedullin) [150], EGR1 [151], TRIB1 [152], SOD2 [153], OXSR1 [154], IL6R [155], CD44 [156], LRG1 [157], PFKFB2 [158], PACSIN2 [159], MYH9 [160], DOT1L [161], CXCL16 [162], PTEN (phosphatase and tensin homolog) [163], FOXO3 [164], DDIT4 [165], PINK1 [166], IQGAP1 [167], ADIPOR1 [168], MTMR3 [169], USF2 [170], SGK1 [171], GSTO2 [172], ETS2 [173], TKT (transketolase) [174], CMIP (c-Maf inducing protein) [175], THBD (granzyme A) [464], IFNG (interferon gamma) [465], IFIH1 [466], STAT1 [467], CCR5 [468], ADCY5 [469], MT2A [470], DPP4 [471], FASLG (Fas ligand)…”

Section: Discussionmentioning

confidence: 99%

“…In the present investigation, a total of 738 DEGs between COVID-19 samples and non COVID-19 samples were identified, consisting of 415 [76], SIGLEC1 [77] and IL1R2 [78] have been suggested to be associated with neurological diseases. CXCL9 [79], SIGLEC1 [80], IL1R2 [81], KLF15 [82] and CD207 [83] [146], STAT4 [147], CXCL8 [148], KLF2 [149], ADM (adrenomedullin) [150], EGR1 [151], TRIB1 [152], SOD2 [153] [162], PTEN (phosphatase and tensin homolog) [163], FOXO3 [164], DDIT4 [165], PINK1 [166], IQGAP1 [167], ADIPOR1 [168], MTMR3 [169] [464], IFNG (interferon gamma) [465], IFIH1 [466], STAT1 [467], CCR5 [468], ADCY5 [469], MT2A [470], DPP4 [471], FASLG (Fas ligand) [472], HLA-DMB [473], CD3D [474], CMKLR1 [475], ICOS (inducible T cell costimulator) [476] [492], CFB (complement factor B) [493], TLR7 [494], SLAMF1 [495], BPIFA1 [496], CD300E [497], TAP2 [498], CD48 [499], APOL1 [500], BACH2 [501], CD226 [502], CXCL12…”

Section: Discussionmentioning

confidence: 99%

Screening key genes and signaling pathways in COVID-19 infection and its associated complications by integrated bioinformatics analysis

Vastrad¹,

Vastrad²

2021

Preprint

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Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2)/ coronavirus disease 2019 (COVID-19) infection is the leading cause of respiratory tract infection associated mortality worldwide. The aim of the current investigation was to identify the differentially expressed genes (DEGs) and enriched pathways in COVID-19 infection and its associated complications by bioinformatics analysis, and to provide potential targets for diagnosis and treatment. Valid next-generation sequencing (NGS) data of 93 COVID 19 samples and 100 non COVID 19 samples (GSE156063) were obtained from the Gene Expression Omnibus database. Gene ontology (GO) and REACTOME pathway enrichment analysis was conducted to identify the biological role of DEGs. In addition, a protein-protein interaction network, modules, miRNA-hub gene regulatory network, TF-hub gene regulatory network and receiver operating characteristic curve (ROC) analysis were used to identify the key genes. A total of 738 DEGs were identified, including 415 up regulated genes and 323 down regulated genes. Most of the DEGs were significantly enriched in immune system process, cell communication, immune system and signaling by NTRK1 (TRKA). Through PPI, modules, miRNA-hub gene regulatory network, TF-hub gene regulatory network analysis, ESR1, UBD, FYN, STAT1, ISG15, EGR1, ARRB2, UBE2D1, PRKDC and FOS were selected as hub genes, which were expressed in COVID-19 samples relative to those in non COVID-19 samples, respectively. Among them, ESR1, UBD, FYN, STAT1, ISG15, EGR1, ARRB2, UBE2D1, PRKDC and FOS were suggested to be diagonstic factors for COVID-19. The findings from this bioinformatics analysis study identified molecular mechanisms and the key hub genes that might contribute to COVID-19 infection and its associated complications.

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“…They are also a potent mediator of primary intracellular reactive oxygen species (ROS). Maintaining mitochondrial function and structure is critical to cellular metabolism, homeostasis, and survival [ 19 ]. The kidney, a high-energy demand organ requiring large quantities of ATP energy to actively maintain its normal function [ 20 ], is rich in mitochondria.…”

Section: Primary Pathogenic Mechanisms Of Ckdmentioning

confidence: 99%

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease

Bean

Liebert

Bicknell

et al. 2022

IJMS

Self Cite

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Chronic kidney disease (CKD) is a growing global public health problem. The implementation of evidence-based clinical practices only defers the development of kidney failure. Death, transplantation, or dialysis are the consequences of kidney failure, resulting in a significant burden on the health system. Hence, innovative therapeutic strategies are urgently needed due to the limitations of current interventions. Photobiomodulation (PBM), a form of non-thermal light therapy, effectively mitigates mitochondrial dysfunction, reactive oxidative stress, inflammation, and gut microbiota dysbiosis, all of which are inherent in CKD. Preliminary studies suggest the benefits of PBM in multiple diseases, including CKD. Hence, this review will provide a concise summary of the underlying action mechanisms of PBM and its potential therapeutic effects on CKD. Based on the findings, PBM may represent a novel, non-invasive and non-pharmacological therapy for CKD, although more studies are necessary before PBM can be widely recommended.

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The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease

Cited by 10 publications

References 86 publications

Src Activation Aggravates Podocyte Injury in Diabetic Nephropathy via Suppression of FUNDC1-Mediated Mitophagy

Src Activation Aggravates Podocyte Injury in Diabetic Nephropathy via Suppression of FUNDC1-Mediated Mitophagy

Screening key genes and signaling pathways in COVID-19 infection and its associated complications by integrated bioinformatics analysis

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease

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