Novel mutation in the <i><scp>TMPRSS</scp>6</i> gene with iron‐refractory iron deficiency anemia

Kodama, Koya; Noguchi, Atsuko; Adachi, Hiroyuki; Hebiguchi, Miwa; Yano, Michihiro; Takahashi, Tsutomu

doi:10.1111/ped.12395

Cited by 16 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hepcidin deficiency increases circulating iron levels in vivo and promotes bone loss in ovariectomized mice (Shen et al 2014, Sun et al 2014). Furthermore, hepcidin overexpression reduces circulating iron levels and retards bone loss, which coincide with Huang's hypothesis (Ma & Xu 2010, Kodama et al 2015, Jiang et al 2016.…”

Section: Discussionsupporting

confidence: 62%

Hepcidin is an endogenous protective factor for osteoporosis by reducing iron levels

Zhang

Wang

et al. 2018

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Postmenopausal osteoporosis is a global health issue. Although a lack of estrogen is considered the major reason for postmenopausal osteoporosis, other factors might also contribute the etiology of the disease. In previous reports, we and others proposed that iron accumulation after menopause accelerates osteoporosis, and here, we genetically modified the expression of an endogenous hormone, hepcidin, to modulate iron status in a mouse model. Our results show that hepcidin levels negatively correlate with bone loss in both knockout and overexpression (with ovariectomy) murine models. In addition, iron overload enhances reactive oxygen species (ROS) activity and attenuates the functions of primary osteoblasts, while iron depletion could reverse this phenomenon through inhibiting the functions of primary osteoclasts. Therefore, our results provide more evidence of the 'iron accumulation' hypothesis, which suggests that high iron levels are risk factors for osteoporosis, and the 'Huang's hypothesis' that hepcidin is a potential drug target for the prevention of postmenopausal osteoporosis.

show abstract

Section: Discussionsupporting

confidence: 62%

Hepcidin is an endogenous protective factor for osteoporosis by reducing iron levels

Zhang

Wang

et al. 2018

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…31,78,79 TMPRSS6 is a negative regulator of hepcidin by cleaving HJV. 80 Tmprss6 deficiency is incapable to promote HJV shedding, leading to excessive Hamp transcription.…”

Section: Iron Disorders Due To Deregulation Of Hepcidinmentioning

confidence: 99%

Hepcidin

et al. 2016

View full text Add to dashboard Cite

Iron is required for most forms of organisms, and it is the most essential element for the functions of many iron-containing proteins involved in oxygen transport, cellular respiration, DNA replication, and so on. Disorders of iron metabolism are associated with diverse diseases, including anemias (e.g., iron-deficiency anemia and anemia of chronic diseases) and iron overload diseases, such as hereditary hemochromatosis and β-thalassemia. Hepcidin (encoded by Hamp gene) is a peptide hormone synthesized by hepatocytes, and it plays an important role in regulating the systematic iron homeostasis. As the systemic iron regulator, hepcidin, not only controls dietary iron absorption and iron egress out of iron storage cells, but also induces iron redistribution in various organs. Deregulated hepcidin is often seen in a variety of iron-related diseases including anemias and iron overload disorders. In the case of iron overload disorders (e.g., hereditary hemochromatosis and β-thalassemia), hepatic hepcidin concentration is significantly reduced.Since hepcidin deregulation is responsible for iron disorder-associated diseases, the purpose of this review is to summarize the recent findings on therapeutics targeting hepcidin.Continuous efforts have been made to search for hepcidin mimics and chemical compounds that could be used to increase hepcidin level. Here, a literature search was conducted in PubMed, and research papers relevant to hepcidin regulation or hepcidin-centered therapeutic work were reviewed. On the basis of literature search, we recapitulated recent findings on therapeutic studies targeting hepcidin, including agonists and antagonists to modulate hepcidin expression or its downstream signaling. We also discussed the molecular mechanisms by which hepcidin level and iron metabolism are modulated.Elevating hepcidin concentration is an optimal strategy to ameliorate iron overload diseases, and also to relieve β-thalassemia phenotypes by improving ineffective erythropoiesis. Relative to the current conventional therapies, such as phlebotomy and blood transfusion, therapeutics targeting hepcidin would open a new avenue for treatment of iron-related diseases.

show abstract

“…However, there are only five cases reported in Asia, including two Chinese female IRIDA patients carrying multiple single nucleotide poymorphisms (SNPs) reported by our hospital (Nie et al , ; Xiong et al , ). Another three cases are from Japan and Korea, carrying homozygous K253E, P354L and G603R mutations, respectively (Sato et al , ; Choi et al , ; Kodama et al , ). Here, we report another Chinese IRIDA case with a novel splicing mutation in combination with two common SNPs in the heterozygous form.…”

Section: Prediction Of Creation Of Potential Splicing Sites In Mutatementioning

confidence: 99%

A novel splicing mutation of TMPRSS6 in a Chinese child with iron‐refractory iron deficiency anaemia

Xiong

Yang

et al. 2015

Br J Haematol

View full text Add to dashboard Cite

Novel mutation in the TMPRSS6 gene with iron‐refractory iron deficiency anemia

Cited by 16 publications

References 23 publications

Hepcidin is an endogenous protective factor for osteoporosis by reducing iron levels

Hepcidin is an endogenous protective factor for osteoporosis by reducing iron levels

Hepcidin

A novel splicing mutation of TMPRSS6 in a Chinese child with iron‐refractory iron deficiency anaemia

Contact Info

Product

Resources

About