Zinc-α2-Glycoprotein Exerts Antifibrotic Effects in Kidney and Heart

被引：38

作者：

Soerensen-Zender, Inga ^{[1
]}

Bhayana, Sagar ^{[1
]}

Susnik, Nathan ^{[1
]}

Rolli, Veronique ^{[5
]}

Batkai, Sandor ^{[4
]}

Baisantry, Arpita ^{[1
,2
]}

Bahram, Siamak ^{[5
]}

Sen, Payel ^{[1
]}

Teng, Beina ^{[1
]}

Lindner, Robert ^{[3
]}

Schiffer, Mario ^{[1
]}

Thum, Thomas ^{[4
,6
]}

Melk, Anette ^{[2
]}

Haller, Hermann ^{[1
]}

Schmitt, Roland ^{[1
]}

机构：

[1] Hannover Med Sch, Integriertes Forsch & Behandlungszentrum Transpla, Dept Nephrol & Hypertens, D-30625 Hannover, Germany

[2] Hannover Med Sch, Integriertes Forsch & Behandlungszentrum Transpla, Dept Pediat Kidney Liver & Metab Dis, D-30625 Hannover, Germany

[3] Hannover Med Sch, Integriertes Forsch & Behandlungszentrum Transpla, Dept Cell Biol, D-30625 Hannover, Germany

[4] Hannover Med Sch, Integriertes Forsch & Behandlungszentrum Transpla, Inst Mol & Translat Therapeut Strategies, D-30625 Hannover, Germany

[5] Hop Univ Strasbourg, Fac Med, Ctr Rech Immunol & Hematol, Immunogenet Mol Humaine, Strasbourg, France

[6] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2015年 / 26卷 / 11期

关键词：

LIPID-MOBILIZING FACTOR; BETA-ADRENERGIC-RECEPTORS; ZINC ALPHA-2-GLYCOPROTEIN; ADIPOKINE ZINC-ALPHA-2-GLYCOPROTEIN; RENAL FIBROSIS; ADIPOSE-TISSUE; SERUM-LEVELS; TGF-BETA; CANCER; ZINC-ALPHA(2)-GLYCOPROTEIN;

D O I：

10.1681/ASN.2014050485

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：

Zinc-alpha 2-glycoprotein (AZGP1) is a secreted protein synthesized by epithelial cells and adipocytes that has roles in lipid metabolism, cell cycling, and cancer progression. Our previous findings in AKI indicated a new role for AZGP1 in the regulation of fibrosis, which is a unifying feature of CKD. Using two models of chronic kidney injury, we now show that mice with genetic AZGP1 deletion develop significantly more kidney fibrosis. This destructive phenotype was rescued by injection of recombinant AZGP1. Exposure of AZGP1-deficient mice to cardiac stress by thoracic aortic constriction revealed that antifibrotic effects were not restricted to the kidney but were cardioprotective. In vitro, recombinant AZG P1 inhibited kidney epithelial dedifferentiation and antagonized fibroblast activation by negatively regulating TGF-beta signaling. Patient sera with high levels of AZGP1 similarly attenuated TGF-beta signaling in fibroblasts. Taken together, these findings indicate a novel role for AZGP1 as a negative regulator of fibrosis progression, suggesting that recombinant AZGP1 may have translational effect for treating fibrotic disease.

引用

页码：2659 / 2668

页数：10

共 43 条

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