Prevention of murine erythropoietic protoporphyria-associated skin photosensitivity and liver disease by dermal and hepatic ferrochelatase.
Prevention of murine erythropoietic protoporphyria-associated skin photosensitivity and liver disease by dermal and hepatic ferrochelatase.
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通过皮肤和肝脏亚铁螯合酶预防小鼠红细胞生成原卟啉症相关的皮肤光敏性和肝脏疾病。
DOI：
10.1111/j.0022-202x.2004.23529.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Leboulch,Philippe
中科院分区：
文献类型：
--
作者：
Pawliuk,Robert;Tighe,Robert;Wise,RobertJ;Mathews-Roth,MichelineM;Leboulch,Philippe
红细胞生成性原卟啉症（EPP）是由亚铁螯合酶缺陷引起的，导致原卟啉主要积聚在红细胞和肝细胞中，并且在血液原卟啉浸出到皮肤中时导致皮肤光敏性。有些患者还出现严重的肝损伤。由于各自的贡献肝和红细胞原卟啉的病理生理学的EPP仍不清楚，我们调查了这个问题，使用小鼠模型的EPP。将EPP小鼠的骨髓移植给正常受体会导致红细胞和血浆原卟啉水平升高。然而，血清肝酶和胆红素的定量以及移植后16个月小鼠肝切片的组织病理学检查均未显示肝损伤的证据。此外，尽管血清原卟啉大量升高，移植小鼠皮肤光敏性的证据很少。光敏性也可以通过将正常小鼠的皮肤移植到EPP受体的背部来局部预防。这些数据验证了毒性原卟啉的主要来源来自红细胞的假设。然而，我们意外地观察到，野生型小鼠的肝细胞和真皮细胞中的正常亚铁螯合酶活性足以预防肝脏疾病和显著的皮肤光敏性。这些发现可能为EPP的治疗提供新的策略。
Erythropoietic protoporphyria (EPP) is caused by a defect in ferrochelatase, leading to the accumulation of protoporphyrin predominantly in erythrocytes and hepatocytes, and resulting in skin photosensitivity upon leaching of blood protoporphyrin into the skin. Some patients also develop severe liver damage. Because the respective contributions of hepatic and erythrocytic protoporphyrin to the pathophysiology of EPP remain unclear, we investigated this question using the murine model of EPP. Transplantation of bone marrow from EPP mice to normal recipients resulted in elevated erythrocyte and plasma protoporphyrin levels. However, quantification of serum liver enzymes and bilirubin together with histopathologic examination of liver sections of mice up to 16 months post-transplantation showed no evidence of liver damage. Moreover, despite massive elevation of serum protoporphyrin, transplanted mice showed minimal evidence of skin photosensitivity. Photosensitivity could also be prevented locally by implanting skin grafts from normal mice onto the backs of EPP recipients. These data validate the hypothesis that the main source of toxic protoporphyrin originates from the erythrocytes. However, we unexpectedly observed that normal ferrochelatase activity in hepatic and dermal cells of wild-type mice is sufficient to prevent liver disease and significant skin photosensitivity. These findings may provide new strategies for the treatment of EPP.
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隐性遗传性铁螯合酶缺乏症伴有贫血、光敏性和肝病
DOI：
--
发表时间：
1991
期刊：
影响因子：
--
作者：
S. Tutois;X. Montagutelli;V. Silva;H. Jouault;P. Rouyer‐Fessard;K. Leroy‐Viard;Jean;Y. Nordmann;Y. Beuzard;Jean
通讯作者：
Jean
β-胡萝卜素治疗红细胞生成性原卟啉症和其他光敏性疾病
影响因子：
--
作者：
M. Mathews;M. Pathak;T. Fitzpatrick;L. Harber;E. Kass
通讯作者：
E. Kass
通过部分基因校正和基于荧光的造血细胞选择，在红细胞生成性原卟啉症小鼠模型中取得了成功的治疗效果
影响因子：
5.1
作者：
A. Fontanellas;M. Méndez;F. Mazurier;M. Cario;S. Navarro;C. Ged;L. Taine;F. Géronimi;E. Richard;F. Moreau;R. Salamanca;H. Verneuil
通讯作者：
H. Verneuil
DOI：
10.1002/lt.500020404
发表时间：
1996
期刊：
Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.
影响因子：
--
作者：
Bloomer,JR;Rank,JM;Payne,WD;Snover,DC;Sharp,HL;Zwiener,RJ;Carithers,RL
通讯作者：
Carithers,RL
红细胞生成性原卟啉症中的铁螯合酶基因突变：关注肝脏疾病。
DOI：
--
发表时间：
2002
期刊：
Cellular and molecular biology (Noisy-le-Grand, France)
影响因子：
--
作者：
Chen,Fu-Ping;Risheg,Hiba;Liu,Yunying;Bloomer,Joseph
通讯作者：
Bloomer,Joseph