Increased calcium uptake and improved trabecular bone properties in intestinal alkaline phosphatase knockout mice

Brun, L.R.; Lombarte, Mercedes; Roma, Stella; Pérez, Fernando; Millán, José Luis; Rigalli, Alfredo

doi:10.1007/s00774-017-0887-7

Cited by 11 publications

(4 citation statements)

References 35 publications

(48 reference statements)

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“…A study conducted in mice completely lacking duodenal IAP (Akp3−/−mice) showed mild atrophy of the villi with a lower absorption surface, resulting in higher calcium uptake than in the control mice. During long-term follow-up, mice lacking IAP had better bone properties than controls, providing evidence that IAP regulates calcium absorption [73].…”

Section: Transport Of Nutrients and Minerals Functionmentioning

confidence: 90%

Intestinal alkaline phosphatase modulation by food components: predictive, preventive, and personalized strategies for novel treatment options in chronic kidney disease

et al. 2020

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Alkaline phosphatase (AP) is a ubiquitous membrane-bound glycoprotein that catalyzes phosphate monoesters' hydrolysis from organic compounds, an essential process in cell signaling. Four AP isozymes have been described in humans, placental AP, germ cell AP, tissue nonspecific AP, and intestinal AP (IAP). IAP plays a crucial role in gut microbial homeostasis, nutrient uptake, and local and systemic inflammation, and its dysfunction is associated with persistent inflammatory disorders. AP is a strong predictor of mortality in the general population and patients with cardiovascular and chronic kidney disease (CKD). However, little is known about IAP modulation and its possible consequences in CKD, a disease characterized by gut microbiota imbalance and persistent low-grade inflammation. Mitigating inflammation and dysbiosis can prevent cardiovascular complications in patients with CKD, and monitoring factors such as IAP can be useful for predicting those complications. Here, we review IAP's role and the results of nutritional interventions targeting IAP in experimental models to prevent alterations in the gut microbiota, which could be a possible target of predictive, preventive, personalized medicine (PPPM) to avoid CKD complications. Microbiota and some nutrients may activate IAP, which seems to have a beneficial impact on health; however, data on CKD remains scarce.

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Section: Transport Of Nutrients and Minerals Functionmentioning

confidence: 90%

Intestinal alkaline phosphatase modulation by food components: predictive, preventive, and personalized strategies for novel treatment options in chronic kidney disease

et al. 2020

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“…More recently, Brun et al showed that Akp3 -/-mice display higher intestinal Ca uptake and Ca retention [51]. Some previous reports indicate that high dietary Ca concentrations decrease Pi digestibility and absorption [52,53].…”

Section: Discussionmentioning

confidence: 99%

A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis

Segawa

Hanazaki

Kirino

et al. 2018

Kidney Blood Press Res

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Background/Aims: Hyperphosphatemia is a serious complication of late-stage chronic kidney disease (CKD). Intestinal inorganic phosphate (Pi) handling plays an important role in Pi homeostasis in CKD. We investigated whether intestinal alkaline phosphatase 3 (Akp3), the enzyme that hydrolyzes dietary Pi compounds, is a target for the treatment of hyperphosphatemia in CKD. Methods: We investigated Pi homeostasis in Akp3 knockout mice (Akp3^-/-). We also studied the progression of renal failure in an Akp3^-/- mouse adenine treated renal failure model. Plasma, fecal, and urinary Pi and Ca concentration were measured with commercially available kit, and plasma fibroblast growth factor 23, parathyroid hormone, and 1,25(OH)₂D₃ concentration were measured with ELISA. Brush border membrane vesicles were prepared from mouse intestine using the Ca²⁺ precipitation method and used for Pi transport activity and alkaline phosphatase activity. In vivo intestinal Pi absorption was measured with oral ³²P administration. Results: Akp3^-/- mice exhibited reduced intestinal type II sodium-dependent Pi transporter (Npt2b) protein levels and Na-dependent Pi co-transport activity. In addition, plasma active vitamin D levels were significantly increased in Akp3^-/- mice compared with wild-type animals. In the adenine-induced renal failure model, Akp3 gene deletion suppressed hyperphosphatemia. Conclusion: The present findings indicate that intestinal Akp3 deletion affects Na⁺-dependent Pi transport in the small intestine. In the adenine-induced renal failure model, Akp3 is predicted to be a factor contributing to suppression of the plasma Pi concentration.

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“…However, accelerated transport of fat droplets through the intestinal epithelium and elevation of serum triglyceride levels were discernible, which was associated with higher intestinal Ca 2+ uptake. [22,23] Overexpression ALPP2…”

Section: Target Gene Outcome (Note) Referencementioning

confidence: 99%

Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm

Saitoh

Kiyokawa

Iwase

et al. 2021

Cells

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Alkaline phosphatase (ALP) is a ubiquitous membrane-bound glycoprotein capable of providing inorganic phosphate by catalyzing the hydrolysis of organic phosphate esters, or removing inorganic pyrophosphate that inhibits calcification. In humans, four forms of ALP cDNA have been cloned, among which tissue-nonspecific ALP (TNSALP) (TNSALP) is widely distributed in the liver, bone, and kidney, making it an important marker in clinical and basic research. Interestingly, TNSALP is highly expressed in juvenile cells, such as pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells (iPSCs)) and somatic stem cells (i.e., neuronal stem cells and bone marrow mesenchymal stem cells). Hypophosphatasia is a genetic disorder causing defects in bone and tooth development as well as neurogenesis. Mutations in the gene coding for TNSALP are thought to be responsible for the abnormalities, suggesting the essential role of TNSALP in these events. Moreover, a reverse-genetics-based study using mice revealed that TNSALP is important in bone and tooth development as well as neurogenesis. However, little is known about the role of TNSALP in the maintenance and differentiation of juvenile cells. Recently, it was reported that cells enriched with TNSALP are more easily reprogrammed into iPSCs than those with less TNSALP. Furthermore, in bone marrow stem cells, ALP could function as a “signal regulator” deciding the fate of these cells. In this review, we summarize the properties of ALP and the background of ALP gene analysis and its manipulation, with a special focus on the potential role of TNSALP in the generation (and possibly maintenance) of juvenile cells.

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Increased calcium uptake and improved trabecular bone properties in intestinal alkaline phosphatase knockout mice

Cited by 11 publications

References 35 publications

Intestinal alkaline phosphatase modulation by food components: predictive, preventive, and personalized strategies for novel treatment options in chronic kidney disease

Intestinal alkaline phosphatase modulation by food components: predictive, preventive, and personalized strategies for novel treatment options in chronic kidney disease

A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis

Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm

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