Endogenous H2S production deficiencies lead to impaired renal erythropoietin production

被引：12

作者：

Leigh, Jennifer ^{[1
,2
]}

Juriasingani, Smriti ^{[1
,2
]}

Akbari, Masoud ^{[1
,2
]}

Shao, Peng ^{[3
]}

Saha, Manujendra N. ^{[2
]}

Lobb, Ian ^{[1
,2
]}

Bachtler, Matthias ^{[4
]}

Fernandez, Bernadette ^{[5
]}

Qian, Zhongming ^{[6
]}

van Goor, Harry ^{[7
,8
]}

Pasch, Andreas ^{[4
,9
]}

Feelisch, Martin ^{[5
]}

Wang, Rui ^{[10
]}

Sener, Alp ^{[1
,2
,11
,12
]}

机构：

[1] Western Univ, Dept Microbiol & Immunol, London, ON, Canada

[2] London Hlth Sci Ctr, Matthew Mailing Ctr Translat Transplant Studies, London, ON, Canada

[3] Western Univ, Dept Physiol, London, ON, Canada

[4] Univ Bern, Dept Clin Res, Bern, Switzerland

[5] Univ Southampton, Southampton Gen Hosp, Fac Med, Clin & Expt Sci, Southampton, Hants, England

[6] Fudan Univ, Lab Neuropharmacol, Sch Pharm, Shanghai, Peoples R China

[7] Univ Groningen, Dept Pathol & Med Biol, Groningen, Netherlands

[8] Univ Med Ctr Groningen, Groningen, Netherlands

[9] Univ Hosp Bern, Dept Clin Chem, Inselspital, Bern, Switzerland

[10] Laurentian Univ, Cardiovasc & Metab Res Unit, Sudbury, ON, Canada

[11] Western Univ, Dept Surg, London, ON, Canada

[12] London Hlth Sci Ctr, Multiorgan Transplant Program, London, ON, Canada

来源：

CUAJ-CANADIAN UROLOGICAL ASSOCIATION JOURNAL | 2019年 / 13卷 / 07期

关键词：

CHRONIC KIDNEY-DISEASE; HYDROGEN-SULFIDE; HYPOXIA; RESPONSES; PATHWAY;

D O I：

10.5489/cuaj.5658

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Introduction: Patients suffering from chronic kidney disease (CKD) experience a number of associated comorbidities, including anemia. Relative deficiency in renal erythropoietin (EPO) production is thought to be a primary cause of anemia. Interestingly, CKD patients display low levels of hydrogen sulfide (H2S), an endogenously derived renal oxygen sensor. Previous in vitro experiments have revealed that H2S-deficient renal cell lines produce less EPO than wild-type renal cell lines during hypoxia. Methods: We postulated that H2S might be a primary mediator of EPO synthesis during hypoxia, which was tested using an in vivo murine model of whole-body hypoxia and in clinical samples obtained from CKD patients. Results: Following a 72-hour period of hypoxia (11% O-2), partial H2S knockout mice (lacking the H2S biosynthetic enzyme cystathionine gamma-lyase [CSE]) displayed lower levels of hemoglobin, EPO, and cystathionine-beta-synthase (CBS) (another H2S biosynthetic enzyme) compared to wild-type mice, all of which was rescued by exogenous H2S supplementation. We also found that anemic CKD patients requiring exogenous EPO exhibited lower urinary thiosulfate levels compared to non-anemic CKD patients of similar CKD classification. Conclusions: Together, our results confirm an interplay between the actions of H2S during hypoxia and EPO production.

引用

页码：E210 / E219

页数：10

共 31 条

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