Cellular communication network 2 (connective tissue growth factor) aggravates acute DNA damage and subsequent DNA damage response-senescence-fibrosis following kidney ischemia reperfusion injury

Valentijn, Floris A.; Knoppert, Sebastiaan N.; Márquez‐Expósito, Laura; Rodrigues-Díez, Raúl R.; Pissas, Georgios; Tang, Jiaqi; Tejedor-Santamaría, Lucía; Broekhuizen, Roel; Samarakoon, Rohan; Eleftheriadis, Theodoros; Goldschmeding, Roel; Nguyen, Tri Q.; Ruíz-Ortega, Marta; Falke, Lucas L.

doi:10.1016/j.kint.2022.06.030

Cited by 12 publications

(20 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is suggested that targeting DNA damage and repair might serve as an attractive tactic to safeguard the kidney in RF and CKD. Cellular communication network factor 2 (CCN2) was detected to exacerbate DNA damage and the consequent DDR-cellular senescence-fibrosis sequence after kidney lesions (73,74). Multiple studies have shown that fatty acids (FA) especially saturated FA are likely to be responsible for the induction of the NLRP3 inflammasome via generating ROS, and more elevated levels of ROS can account for oxidative DNA damage (75,76).…”

Section: Dna Damagesmentioning

confidence: 99%

Cellular senescence of renal tubular epithelial cells in renal fibrosis

Zhang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

Renal fibrosis (RF) is the common pathological manifestation of virtually all chronic kidney diseases (CKD) and one of the major causes of end-stage renal disease (ESRD), but the pathogenesis of which is still unclear. Renal tubulointerstitial lesions have been identified as a key pathological hallmark of RF pathology. Renal tubular epithelial cells are the resident cells of the tubulointerstitium and play an important role in kidney recovery versus renal fibrosis following injury. Studies in recent years have shown that senescence of renal tubular epithelial cells can accelerate the progression of renal fibrosis. Oxidative stress(OS), telomere attrition and DNA damage are the major causes of renal tubular epithelial cell senescence. Current interventions and therapeutic strategies for cellular senescence include calorie restriction and routine exercise, Klotho, senolytics, senostatics, and other related drugs. This paper provides an overview of the mechanisms and the key signaling pathways including Wnt/β-catenin/RAS, Nrf2/ARE and STAT-3/NF-κB pathway involved in renal tubular epithelial cell senescence in RF and therapies targeting renal tubular epithelial cell senescence future therapeutic potential for RF patients. These findings may offer promise for the further treatment of RF and CKD.

show abstract

Section: Dna Damagesmentioning

confidence: 99%

Cellular senescence of renal tubular epithelial cells in renal fibrosis

Zhang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Recent preclinical research has shown the important role of cellular and molecular senescence-related mechanisms in natural aging, AKI and in the AKI-to-CKD transition [ 2 , 38 , 39 , 40 , 41 ]. In C57BL/6 mice, natural aging was characterized by decreased Klotho gene expression and activation of DDR in the kidneys as soon as 12 months.…”

Section: Ckd and Cellular Senescencementioning

confidence: 99%

“…Preclinical studies in different AKI models have described early cellular senescence activation, including upregulation of p21 expression. Moreover, treatment with a p53 inhibitor in IRI has demonstrated the importance of G1 cell cycle arrest in the AKI-to-CKD transition and progression of fibrosis [ 38 , 39 , 40 , 41 ]. Future studies are still needed to unravel the cellular and molecular mechanisms involved in kidney injury and repair, including the failure of the repair process.…”

Section: Ckd and Cellular Senescencementioning

confidence: 99%

“…In this sense, IRI studies in CCN2-deleted mice showed that CCN2 is a part of the SASP secretome that could also trigger senescence by itself. In cultured murine tubular epithelial cells, stimulation with CCN2 induced a senescent cellular phenotype [ 38 ]. In addition, human kidney grafts showed increased CCA-related proteins associated with the upregulation of CCN2 protein, confirming the clinical relevance of murine studies [ 38 ].…”

Section: Ckd and Cellular Senescencementioning

confidence: 99%

“…In cultured murine tubular epithelial cells, stimulation with CCN2 induced a senescent cellular phenotype [ 38 ]. In addition, human kidney grafts showed increased CCA-related proteins associated with the upregulation of CCN2 protein, confirming the clinical relevance of murine studies [ 38 ]. However, additional preclinical studies are necessary to evaluate the extent to which targeting senescence in CKD or kidney grafts decreases fibrosis and improves kidney function and graft survival.…”

Section: Ckd and Cellular Senescencementioning

confidence: 99%

See 2 more Smart Citations

Vitamin D, Cellular Senescence and Chronic Kidney Diseases: What Is Missing in the Equation?

et al. 2023

Self Cite

View full text Add to dashboard Cite

As life expectancy increases in many countries, the prevalence of age-related diseases also rises. Among these conditions, chronic kidney disease is predicted to become the second cause of death in some countries before the end of the century. An important problem with kidney diseases is the lack of biomarkers to detect early damage or to predict the progression to renal failure. In addition, current treatments only retard kidney disease progression, and better tools are needed. Preclinical research has shown the involvement of the activation of cellular senescence-related mechanisms in natural aging and kidney injury. Intensive research is searching for novel treatments for kidney diseases as well as for anti-aging therapies. In this sense, many experimental shreds of evidence support that treatment with vitamin D or its analogs can exert pleiotropic protective effects in kidney injury. Moreover, vitamin D deficiency has been described in patients with kidney diseases. Here, we review recent evidence about the relationship between vitamin D and kidney diseases, explaining the underlying mechanisms of the effect of vitamin D actions, with particular attention to the modulation of cellular senescence mechanisms.

show abstract

Epithelial–mesenchymal plasticity in kidney fibrosis

Hadpech

Thongboonkerd

2023

Genesis

View full text Add to dashboard Cite

SummaryEpithelial–mesenchymal transition (EMT) is an important biological process contributing to kidney fibrosis and chronic kidney disease. This process is characterized by decreased epithelial phenotypes/markers and increased mesenchymal phenotypes/markers. Tubular epithelial cells (TECs) are commonly susceptible to EMT by various stimuli, for example, transforming growth factor‐β (TGF‐β), cellular communication network factor 2, angiotensin‐II, fibroblast growth factor‐2, oncostatin M, matrix metalloproteinase‐2, tissue plasminogen activator (t‐PA), plasmin, interleukin‐1β, and reactive oxygen species. Similarly, glomerular podocytes can undergo EMT via these stimuli and by high glucose condition in diabetic kidney disease. EMT of TECs and podocytes leads to tubulointerstitial fibrosis and glomerulosclerosis, respectively. Signaling pathways involved in EMT‐mediated kidney fibrosis are diverse and complex. TGF‐β1/Smad and Wnt/β‐catenin pathways are the major venues triggering EMT in TECs and podocytes. These two pathways thus serve as the major therapeutic targets against EMT‐mediated kidney fibrosis. To date, a number of EMT inhibitors have been identified and characterized. As expected, the majority of these EMT inhibitors affect TGF‐β1/Smad and Wnt/β‐catenin pathways. In addition to kidney fibrosis, these EMT‐targeted antifibrotic inhibitors are expected to be effective for treatment against fibrosis in other organs/tissues.

show abstract

Cellular communication network 2 (connective tissue growth factor) aggravates acute DNA damage and subsequent DNA damage response-senescence-fibrosis following kidney ischemia reperfusion injury

Cited by 12 publications

References 55 publications

Cellular senescence of renal tubular epithelial cells in renal fibrosis

Cellular senescence of renal tubular epithelial cells in renal fibrosis

Vitamin D, Cellular Senescence and Chronic Kidney Diseases: What Is Missing in the Equation?

Epithelial–mesenchymal plasticity in kidney fibrosis

Contact Info

Product

Resources

About