Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease

Kashyap, Sonu; Zeidler, Julianna D.; Chini, Claudia C.S.; Chini, Eduardo N.

doi:10.1016/j.cellsig.2020.109698

Cited by 8 publications

(5 citation statements)

References 165 publications

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“…Additionally, Kashyap et al identified a role of IGF pathways in ADPKD pathogenesis. PAPP-A, a component of the IGF pathway that increases the bioavailability of IGF-1, was highly expressed in kidneys of PKD1-deficient mice and also in cystic fluids and kidneys of humans with ADPKD [68,69]. In this study, PAPP-A deficiency decreased the development of cysts in ADPKD mice, and treatment of mice with a monoclonal antibody that blocks the proteolytic activity of PAPP-A was associated with a decreased cystic burden [68].…”

Section: Data From Animal Modelssupporting

confidence: 52%

Is autosomal dominant polycystic kidney disease an early sweet disease?

et al. 2022

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The clinical course of autosomal dominant polycystic kidney disease (ADPKD) starts in childhood. Evidence of the beneficial impact of early nephron-protective strategies and lifestyle modifications on ADPKD prognosis is accumulating. Recent studies have described the association of overweight and obesity with rapid disease progression in adults with ADPKD. Moreover, defective glucose metabolism and metabolic reprogramming have been reported in distinct ADPKD models highlighting these pathways as potential therapeutic targets in ADPKD. Several "metabolic" approaches are currently under evaluation in adults, including ketogenic diet, food restriction, and metformin therapy. No data are available on the impact of these approaches in childhood thus far. Yet, according to World Health Organization (WHO), we are currently facing a childhood obesity crisis with an increased prevalence of overweight/obesity in the pediatric population associated with a cardio-metabolic risk profile. The present review summarizes the knowledge about the role of glucose metabolism in the pathophysiology of ADPKD and underscores the possible harm of overweight and obesity in ADPKD especially in terms of long-term cardiovascular outcomes and renal prognosis.

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Section: Data From Animal Modelssupporting

confidence: 52%

Is autosomal dominant polycystic kidney disease an early sweet disease?

et al. 2022

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“…PAPP-A primarily cleaves IGFBP4 and IGFBP5 (Conover and Oxvig, 2018;Laursen et al, 2007;Oxvig, 2015). A number of studies indicate a local role of STC1 in the kidney (Kashyap et al, 2020b). Genome-wide association studies have identified STC1 as one of the chronic kidney disease genes (Böger and Heid, 2011).…”

Section: Discussionmentioning

confidence: 99%

Stanniocalcin 1a is a Ca²⁺-regulated switch controlling epithelial cell quiescence-proliferation balance and Ca²⁺uptake

Liu

Goldstein

et al. 2020

Preprint

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The mechanisms governing cell quiescence-proliferation balance are poorly defined. Using a zebrafish model, here we report that Stc1a, a glycoprotein known as a hypocalcemic hormone, not only inhibits epithelial calcium uptake but also functions as a Ca2+-regulated switch controlling epithelial cell quiescence-proliferation balance. Among the 4 stc genes, only the stc1a expression is [Ca2+]-dependent. Genetic deletion of stc1a, but not stc2b, resulted in elevated body Ca2+ contents, ectopic Ca2+ deposit, body swelling, and premature death. Reducing epithelial calcium channel Trpv6-mediated Ca2+ uptake alleviated these phenotypes. Loss of Stc1a also promoted quiescent epithelial cells to re-enter the cell cycle. This action was accompanied by local IGF signaling activation and increased expression in papp-aa, a zinc metalloproteinase degrading Igfbp5a. Genetic deletion of papp-aa or igfbp5a abolished the elevated epithelial cell reactivation in stc1a−/− mutants. Likewise, inhibition of IGF1 receptor, PI3 kinase, Akt, and Tor signaling abolished epithelial cell reactivation. These results reveal that Stc1a plays dual roles in regulating epithelial calcium uptake and cell quiescence-proliferation balance and implicate Trpv6 and Papp-aa-Igfbp5a-IGF signaling in these functions.

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“…The beneficial effects of food restriction in several aspects of health appears to be related to the insulin growth factor-1 (IGF-1) pathway, which is also dysregulated in cancer and aging. In ADPKD, IGF-1 could be involved in cyst proliferation; in fact, some studies have found increased expression of IGF-1 in polycystic patients and animal models [47]. The work of S. Kashyap et al [48] identified PAPP-A, a metalloprotease that cleaves IGF-1 binding protein and frees IFG-1, as a crucial factor in increasing IGF-1 bioavailability and which opens new future research for understanding ADPKD pathological mechanisms and for discovering new therapeutic targets.…”

Section: Calories and Body Weightmentioning

confidence: 99%

Diet and Physical Activity in Adult Dominant Polycystic Kidney Disease: A Review of the Literature

Capelli,

Lerario,

Aiello

et al. 2023

Nutrients

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Autosomal polycystic kidney disease is the most common inherited kidney disease determining 5% of all end-stage kidney disease. The only therapy approved for this condition is Tolvaptan, which, with its aquaretic effect, has a strong effect on patients’ daily life. Recently, the literature has been enriched with new works that analyze possible non-pharmacological therapeutic strategies to slow cysts’ enlargement and chronic kidney disease progression. Among them, dietary schemes reducing carbohydrate intake and inducing ketoses have been demonstrated to have efficacy in several pre-clinical and clinical studies. A ketogenic diet, calorie restriction, intermittent fasting, and time-restricted feeding can reduce aerobic glycolysis and inhibit the mTOR pathway, producing a reduction in cyst cell proliferation, a reduction in kidney volume, and helping to preserve kidney function. ADPKD’s burden of disease has an impact on patients’ quality of life, and the possibility to play sports or carry out physical exercise can help people in everyday life. The multisystemic character of the disease, especially cardiovascular involvement, needs to be carefully evaluated to establish the quality and quantity of physical activity that patients can safely carry out.

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Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease

Cited by 8 publications

References 165 publications

Is autosomal dominant polycystic kidney disease an early sweet disease?

Is autosomal dominant polycystic kidney disease an early sweet disease?

Stanniocalcin 1a is a Ca²⁺-regulated switch controlling epithelial cell quiescence-proliferation balance and Ca²⁺uptake

Diet and Physical Activity in Adult Dominant Polycystic Kidney Disease: A Review of the Literature

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Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease

Cited by 8 publications

References 165 publications

Is autosomal dominant polycystic kidney disease an early sweet disease?

Is autosomal dominant polycystic kidney disease an early sweet disease?

Stanniocalcin 1a is a Ca2+-regulated switch controlling epithelial cell quiescence-proliferation balance and Ca2+uptake

Diet and Physical Activity in Adult Dominant Polycystic Kidney Disease: A Review of the Literature

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Stanniocalcin 1a is a Ca²⁺-regulated switch controlling epithelial cell quiescence-proliferation balance and Ca²⁺uptake