Cholecystokinin Plays a Novel Protective Role in Diabetic Kidney Through Anti-inflammatory Actions on Macrophage Anti-inflammatory Effect of Cholecystokinin

被引：66

作者：

Miyamoto, Satoshi ^{[1
]}

Shikata, Kenichi ^{[1
,2
]}

Miyasaka, Kyoko ^{[3
]}

Okada, Shinichi ^{[1
]}

Sasaki, Motofumi ^{[1
]}

Kodera, Ryo ^{[1
,2
]}

Hirota, Daisho ^{[1
]}

Kajitani, Nobuo ^{[1
]}

Takatsuka, Tetsuharu ^{[1
]}

Kataoka, Hitomi Usui ^{[1
,4
]}

Nishishita, Shingo ^{[1
]}

Sato, Chikage ^{[1
,5
]}

Funakoshi, Akihiro ^{[6
]}

Nishimori, Hisakazu ^{[7
]}

Uchida, Haruhito Adam ^{[1
]}

Ogawa, Daisuke ^{[1
,5
]}

Makino, Hirofumi ^{[1
]}

机构：

[1] Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

[2] Okayama Univ Hosp, Ctr Innovat Clin Med, Okayama, Japan

[3] Tokyo Kasei Univ, Dept Nutr & Physiol, Tokyo, Japan

[4] Okayama Univ, Dept Primary Care & Med Educ, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

[5] Okayama Univ, Dept Diabet Nephropathy, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

[6] Kyushu Natl Canc Ctr, Dept Gastroenterol, Fukuoka, Japan

[7] Okayama Univ, Dept Hematol & Oncol, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

来源：

DIABETES | 2012年 / 61卷 / 04期

关键词：

NF-KAPPA-B; PULMONARY INTERSTITIAL MACROPHAGES; INTERCELLULAR-ADHESION MOLECULE-1; CCK-A RECEPTOR; MONOCYTE MIGRATION; ANGIOTENSIN-II; EXPRESSION; NEPHROPATHY; MICE; RAT;

D O I：

10.2337/db11-0402

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Inflammatory process is involved in the pathogenesis of diabetic nephropathy. In this article, we show that cholecystokinin (CCK) is expressed in the kidney and exerts renoprotective effects through its anti-inflammatory actions. DNA microarray showed that CCK was upregulated in the kidney of diabetic wild-type (WT) mice but not in diabetic intracellular adhesion molecule-1 knockout mice. We induced diabetes in CCK-1 receptor (CCK-1R) and CCK-2R double-knockout (CCK-1R(-/-),-2R(-/-)) mice, and furthermore, we performed a bone marrow transplantation study using CCK-1R(-/-) mice to determine the role of CCK-1R on macrophages in the diabetic kidney. Diabetic CCK-1R(-/-),-2R(-/-) mice revealed enhanced albuminuria and inflammation in the kidney compared with diabetic WT mice. In addition, diabetic WT mice with CCK-1R(-/-) bone marrow-derived cells developed more albuminuria than diabetic CCK-1R(-/-) mice with WT bone marrow-derived cells. Administration of sulfated cholecystokinin octapeptide (CCK-8S) ameliorated albuminuria, podocyte loss, expression of proinflammatory genes, and infiltration of macrophages in the kidneys of diabetic rats. Furthermore, CCK-8S inhibited both expression of tumor necrosis factor-alpha and chemotaxis in cultured THP-1 cells. These results suggest that CCK suppresses the activation of macrophage and expression of proinflammatory genes in diabetic kidney. Our findings may provide a novel strategy of therapy for the early stage of diabetic nephropathy. Diabetes 61:897-907, 2012

引用

页码：897 / 907

页数：11

共 45 条

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