Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis

Renal fibrosis is a devastating consequence of progressive chronic kidney disease, representing a major public health challenge worldwide. The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear, and effective treatments are still lacking. Renal tubular epithelial cells (RTECs) maintain kidney function, and their dysfunction has emerged as a critical contributor to renal fibrosis. Cellular quality control comprises several components, including telomere homeostasis, ubiquitin-proteasome system (UPS), autophagy, mitochondrial homeostasis (mitophagy and mitochondrial metabolism), endoplasmic reticulum (ER, unfolded protein response), and lysosomes. Failures in the cellular quality control of RTECs, including DNA, protein, and organelle damage, exert profibrotic functions by leading to senescence, defective autophagy, ER stress, mitochondrial and lysosomal dysfunction, apoptosis, fibroblast activation, and immune cell recruitment. In this review, we summarize recent advances in understanding the role of quality control components and intercellular crosstalk networks in RTECs, within the context of renal fibrosis.

• Publication year

  2024

• Venue

  Journal of Pharmaceutical Analysis

• Publication date

  2024-01-01

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1016/j.jpha.2024.01.001PMID 39247486PMCID 11377145
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Kidney fibrosis: from mechanisms to therapeutic medicines

  2023cited by this paper
• Exosomes from tubular epithelial cells undergoing epithelial‐to‐mesenchymal transition promote renal fibrosis by M1 macrophage activation

  2023cited by this paper
• Cellular senescence of renal tubular epithelial cells in renal fibrosis

  2023cited by this paper
• TFEB-mediated lysosomal exocytosis alleviates high-fat diet–induced lipotoxicity in the kidney

  2023cited by this paper
• Unconventional Initiation of PINK1/Parkin Mitophagy by Optineurin

  2023cited by this paper
• Renal tubular epithelial cells are constitutive non-cognate stimulators of resident T cells.

  2023cited by this paper
• Ubiquitin-like protein FAT10 promotes renal fibrosis by stabilizing USP7 to prolong CHK1-mediated G2/M arrest in renal tubular epithelial cells

  2022cited by this paper
• The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis

  2022cited by this paper
• New insights into fibrosis from the ECM degradation perspective: the macrophage-MMP-ECM interaction

  2022cited by this paper
• The fibrogenic niche in kidney fibrosis: components and mechanisms

  2022cited by this paper
• Targeting fibrosis: mechanisms and clinical trials

  2022cited by this paper
• The down-regulation of XBP1, an unfolded protein response effector, promotes acute kidney injury to chronic kidney disease transition

  2022cited by this paper
• Autophagy and Renal Fibrosis

  2022cited by this paper
• The pathological role of damaged organelles in renal tubular epithelial cells in the progression of acute kidney injury

  2022cited by this paper
• Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis

  2022cited by this paper
• Mitochondrial quality control in health and in Parkinson's disease.

  2022cited by this paper
• Targeting TGF-β signal transduction for fibrosis and cancer therapy

  2022cited by this paper
• Reshaping endoplasmic reticulum quality control through the unfolded protein response.

  2022cited by this paper
• CircACTR2 in macrophages promotes renal fibrosis by activating macrophage inflammation and epithelial–mesenchymal transition of renal tubular epithelial cells

  2022cited by this paper
• Corrigendum to “Upregulation of TIPE1 in tubular epithelial cell aggravates diabetic nephropathy by disrupting PHB2 mediated mitophagy” [Redox Biol. 50 (2022) 2213–2317/102260]

  2022cited by this paper
• Quality control of protein complex assembly by the ubiquitin-proteasome system.

  2022cited by this paper
• Driving role of macrophages in transition from acute kidney injury to chronic kidney disease

  2022cited by this paper
• Nuclear farnesoid X receptor attenuates acute kidney injury through fatty acid oxidation.

  2022cited by this paper
• Telomere dysfunction in ageing and age-related diseases

  2022cited by this paper
• MiR-155 deficiency protects renal tubular epithelial cells from telomeric and genomic DNA damage in cisplatin-induced acute kidney injury

  2022cited by this paper
• VHL-recruiting PROTAC attenuates renal fibrosis and preserves renal function via simultaneous degradation of Smad3 and stabilization of HIF-2α

  2022cited by this paper
• Tubule epithelial cells and fibroblasts communication: Vicious cycle of renal fibrosis

  2022cited by this paper
• Leukemia inhibitory factor is a therapeutic target for renal interstitial fibrosis

  2022cited by this paper
• Spatial dynamic metabolomics identifies metabolic cell fate trajectories in human kidney differentiation.

  2022cited by this paper
• A new LKB1 activator, piericidin analogue S14, retards renal fibrosis through promoting autophagy and mitochondrial homeostasis in renal tubular epithelial cells

  2022cited by this paper
• Telomerase is required for glomerular renewal in kidneys of adult mice

  2022cited by this paper
• Upregulation of TIPE1 in tubular epithelial cell aggravates diabetic nephropathy by disrupting PHB2 mediated mitophagy

  2022cited by this paper
• Tubular epithelial cell-to-macrophage communication forms a negative feedback loop via extracellular vesicle transfer to promote renal inflammation and apoptosis in diabetic nephropathy

  2022cited by this paper
• Mechanisms and Regulation of Cellular Senescence

  2021cited by this paper
• -Dysregulation of the sensory and regulatory pathways controlling cellular iron metabolism in unilateral obstructive nephropathy.

  2021cited by this paper
• PTEN alleviates maladaptive repair of renal tubular epithelial cells by restoring CHMP2A-mediated phagosome closure

  2021cited by this paper
• Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis.

  2021cited by this paper
• Stress and telomere shortening: Insights from cellular mechanisms

  2021cited by this paper
• Relationship between lysosomal dyshomeostasis and progression of diabetic kidney disease

  2021cited by this paper
• AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice

  2021cited by this paper
• Autophagy in major human diseases

  2021cited by this paper
• MHC class II in renal tubules plays an essential role in renal fibrosis

  2021cited by this paper
• Dynamic EMT: a multi‐tool for tumor progression

  2021cited by this paper
• Defining therapeutic targets for renal fibrosis: Exploiting the biology of pathogenesis.

  2021cited by this paper
• Vitamin D-VDR (vitamin D receptor) regulates defective autophagy in renal tubular epithelial cell in streptozotocin-induced diabetic mice via the AMPK pathway

  2021cited by this paper
• Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis.

  2021cited by this paper
• Prospective Pharmacological Potential of Resveratrol in Delaying Kidney Aging

  2021cited by this paper
• The Role of Macrophages in Kidney Fibrosis

  2021cited by this paper
• Brahma-related gene-1 promotes tubular senescence and renal fibrosis through Wnt/β-catenin/autophagy axis

  2021cited by this paper
• Multifunctionality of the Telomere-Capping Shelterin Complex Explained by Variations in Its Protein Composition

  2021cited by this paper
• Fibroblasts: Origins, definitions, and functions in health and disease.

  2021cited by this paper
• Phosphoproteomic identification of ULK substrates reveals VPS15‐dependent ULK/VPS34 interplay in the regulation of autophagy

  2021cited by this paper
• Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease

  2021cited by this paper
• Role of lysosomes in physiological activities, diseases, and therapy

  2021cited by this paper
• MiT Family Transcriptional Factors in Immune Cell Functions

  2021cited by this paper
• Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing

  2021cited by this paper
• Telomere shortening promotes kidney fibrosis

  2021cited by this paper
• Oxidative Stress Is Associated with Telomere Interaction Impairment and Chromatin Condensation Defects in Spermatozoa of Infertile Males

  2021cited by this paper
• Epithelial proliferation and cell cycle dysregulation in kidney injury and disease.

  2021cited by this paper
• Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype

  2021cited by this paper
• Epithelial plasticity, epithelial-mesenchymal transition, and the TGF-β family.

  2021cited by this paper
• Molecular mechanisms and physiological functions of mitophagy

  2021cited by this paper
• Targeting unfolded protein response: a new horizon for disease control

  2021cited by this paper
• Renovascular Disease Induces Senescence in Renal Scattered Tubular-Like Cells and Impairs Their reparative Potency.

  2021cited by this paper
• HIF-1α-BNIP3-mediated mitophagy in tubular cells protects against renal ischemia/reperfusion injury

  2020cited by this paper
• The emerging role of cellular senescence in renal diseases

  2020cited by this paper
• ATF6 Is a Critical Determinant of CHOP Dynamics during the Unfolded Protein Response

  2020cited by this paper
• Immune cell landscaping reveals a protective role for regulatory T cells during kidney injury and fibrosis.

  2020cited by this paper
• Stress-induced tyrosine phosphorylation of RtcB modulates IRE1 activity and signaling outputs

  2020cited by this paper
• Sirt3 modulates fatty acid oxidation and attenuates cisplatin‐induced AKI in mice

  2020cited by this paper
• Guidelines and definitions for research on epithelial–mesenchymal transition

  2020cited by this paper
• Mitochondrial Metabolism in Acute Kidney Injury.

  2020cited by this paper
• Injured tubular epithelial cells activate fibroblasts to promote kidney fibrosis through miR-150-containing exosomes.

  2020cited by this paper
• Emerging roles of ATG proteins and membrane lipids in autophagosome formation

  2020cited by this paper
• Decoy receptor 2 mediation of the senescent phenotype of tubular cells by interacting with peroxiredoxin 1 presents a novel mechanism of renal fibrosis in diabetic nephropathy.

  2020cited by this paper
• Telomere transcription in Ageing.

  2020cited by this paper
• Ginsenoside Rb1 ameliorates autophagy via the AMPK/mTOR pathway in renal tubular epithelial cells in vitro and in vivo.

  2020cited by this paper
• Quercetin alleviates kidney fibrosis by reducing renal tubular epithelial cell senescence through the SIRT1/PINK1/mitophagy axis.

  2020cited by this paper
• Recent Advances in the Role of Natural Killer Cells in Acute Kidney Injury

  2020cited by this paper
• p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease.

  2020cited by this paper
• PINK1: The guard of mitochondria.

  2020cited by this paper
• The Roles of Immune Cells in the Pathogenesis of Fibrosis

  2020cited by this paper
• The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases

  2020cited by this paper
• Two identified subsets of CD8 T cells in obstructed kidneys play different roles in inflammation and fibrosis

  2020cited by this paper
• Mitophagy pathways in health and disease

  2020cited by this paper
• GLP-1 Alleviates Diabetic Kidney Disease Through Activation of Autophagy by Regulating AMPK/mTOR Pathway.

  2020cited by this paper
• SMAD3 promotes autophagy dysregulation by triggering lysosome depletion in tubular epithelial cells in diabetic nephropathy

  2020cited by this paper
• Composition and Function of Telomerase—A Polymerase Associated with the Origin of Eukaryotes

  2020cited by this paper
• Sodium-Glucose Co-Transporter 2 Inhibitors Correct Metabolic Maladaptation of Proximal Tubular Epithelial Cells in High-Glucose Conditions

  2020cited by this paper
• Lipids and membrane-associated proteins in autophagy

  2020cited by this paper
• Swainsonine promotes apoptosis by inhibiting autophagic degradation via impairing lysosomal function in primary renal tubular epithelial cells of rats.

  2020cited by this paper
• Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis

  2020cited by this paper
• Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies

  2020cited by this paper
• AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney Injury

  2020cited by this paper
• Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of HIF1A and BNIP3-mediated mitophagy

  2020cited by this paper
• Functional Modules of the Proteostasis Network.

  2019cited by this paper
• Role of Endoplasmic Reticulum Stress in the Anticancer Activity of Natural Compounds

  2019cited by this paper
• Lysosomes as dynamic regulators of cell and organismal homeostasis

  2019cited by this paper
• Mitophagy: a crucial modulator in the pathogenesis of chronic diseases.

  2019cited by this paper
• Cellular quality control by the ubiquitin-proteasome system and autophagy

  2019cited by this paper

• Critical Role of Pyroptosis in Deoxynivalenol-Induced Renal Tubular Epithelial Damage in Mice.

  2026cites this paper
• QingShen Granules Activates Mitophagy to Suppress Renal Tubular Epithelial-Mesenchymal Transition via the miR-23b-5p/Nrf2/PINK1 Axis.

  2026cites this paper
• Huaier-derived neutral polysaccharide WHPB mitigates renal fibrosis via CSF-1R/PI3K/AKT-mediated FUT8 inhibition.

  2026cites this paper
• The Limb-bud and Heart (LBH) promotes renal fibrosis through endoplasmic reticulum stress-induced pyroptosis and partial epithelial-mesenchymal transition in renal tubular epithelial cells.

  2026cites this paper
• UBR4 Attenuates Cisplatin-Induced Acute Kidney Injury by Regulating the HRI-ISR Axis.

  2026cites this paper
• Endoplasmic reticulum stress and the unfolded protein response in ischemic nephropathy: Pathogenic mechanisms and emerging therapeutic strategies.

  2026cites this paper
• Delactylase effects of SIRT3 on a positive feedback loop involving the RUNX1-glycolysis-histone lactylation in diabetic kidney disease

  2026cites this paper
• Shen-Shuai-Ⅱ Recipe ameliorates chronic kidney disease-induced myocardial injury via inhibition of the IL-18/IL-18R1/MyD88 pathway.

  2026cites this paper
• Targeting renal tubular epithelial cells via a dual functionalized oligosaccharide self-assembly in the management of acute and chronic kidney diseases

  2025cites this paper
• Breaking the fibrotic code: Nanotechnology-driven advances in renal fibrosis therapy.

  2025cites this paper
• Autophagy–senescence interplay in kidney disease: mechanistic insights and therapeutic potential

  2025cites this paper
• Ferroptosis in Tubular Epithelial Cells Across Distinct Renal Regions Is a Primary Causal Factor for Lupus Nephritis

  2025cites this paper
• Inhibition of FXIIa attenuates kidney fibrosis in mice with unilateral ureteral obstruction

  2025cites this paper
• Oxidative Stress and Inflammation in Renal Fibrosis: Novel Molecular Mechanisms and Therapeutic Targets.

  2025cites this paper
• Plumbagin ameliorates renal fibrosis by suppressing epithelial-mesenchymal transition.

  2025cites this paper
• Research dynamics and drug treatment of renal fibrosis from a mitochondrial perspective: a historical text data analysis based on bibliometrics

  2025cites this paper
• Clerodendranthus spicatus-Cordyceps cicadae regulates mitophagy and protects renal tubular epithelial cells from hyperuricemic nephropathy.

  2025cites this paper
• Aptamer-targeted anti-miR RNA construct based on 3WJ as a new approach for the treatment of chronic kidney disease in an experimental model

  2025cites this paper
• Prognostic implications of systemic immune-inflammation index and systemic inflammation response index in hemodialysis patients

  2025cites this paper
• Role of Metabolic Abnormalities During the Progression of Chronic Kidney Disease and Preventive Strategies

  2025cites this paper
• Norepinephrine ameliorates sepsis-associated acute kidney injury through inhibiting damage of renal tubular epithelium induced by macrophage inflammatory response

  2025cites this paper
• Augmenter of liver regeneration inhibits renal fibrosis during acute kidney injury to chronic kidney disease transition by regulating autophagic flux.

  2024cites this paper
• Induction of GPX4-regulated ferroptotic stress promotes epithelial-to-mesenchymal transition in renal tubule cells induced by PM2.5.

  2024cites this paper