Diabetes Aggravates Postischaemic Renal Fibrosis through Persistent Activation of TGF-β1 and Shh Signalling

被引：16

作者：

Kim, Dong-Jin ^{[2
,3
]}

Kang, Jun Mo ^{[4
]}

Park, Seon Hwa ^{[1
]}

Kwon, Hyuk-Kwon ^{[1
]}

Song, Seok-Jong ^{[1
]}

Moon, Haena ^{[1
]}

Kim, Su-Mi ^{[1
]}

Seo, Jung-Woo ^{[1
]}

Lee, Yu Ho ^{[1
]}

Kim, Yang Gyun ^{[1
]}

Moon, Ju-Young ^{[1
]}

Lee, So-Young ^{[4
]}

Son, Youngsook ^{[2
,3
]}

Lee, Sang-Ho ^{[1
]}

机构：

[1] Kyung Hee Univ, Kyung Hee Univ Hosp Gangdong, Div Nephrol, Dept Internal Med,Coll Med, Seoul, South Korea

[2] Kyung Hee Univ, Coll Life Sci, Dept Genet Engn, Global Campus, Yongin, South Korea

[3] Kyung Hee Univ, Grad Sch Biotechnol, Global Campus, Yongin, South Korea

[4] CHA Univ, CHA Bundang Med Ctr, Dept Internal Med, Div Nephrol, Seongnam, South Korea

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

新加坡国家研究基金会;

关键词：

GROWTH-FACTOR-BETA; EPITHELIAL-MESENCHYMAL TRANSITION; SONIC HEDGEHOG; MOLECULAR-MECHANISMS; PATHWAY ACTIVATION; T-CELLS; KIDNEY; INJURY; RECRUITMENT; MYOFIBROBLASTS;

D O I：

10.1038/s41598-017-16977-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Diabetes is a risk factor for acute kidney injury (AKI) and chronic kidney disease (CKD). Diabetic patients are easy to progress to CKD after AKI. Currently, activation of fibrotic signalling including transforming growth factor-beta(1) (TGF-beta(1)) is recognized as a key mechanism in CKD. Here, we investigated the influence of diabetes on CKD progression after AKI by using a unilateral renal ischaemia-reperfusion injury (IRI) model in diabetic mice. IRI induced extensive tubular injury, fibrosis and lymphocyte recruitment at 3 weeks after IRI, irrespective of diabetes. However, diabetes showed sustained tubular injury and markedly increased fibrosis and lymphocyte recruitment compared with non-diabetes at 5 week after IRI. The mRNAs and proteins related to TGF-beta(1) and sonic hedgehog (Shh) signalling were significantly higher in diabetic versus non-diabetic IRI kidneys. During the in vitro study, the hyperglycaemia induced the activation of TGF-beta(1) and Shh signalling and also increased profibrogenic phenotype change. However, hyperglycaemic control with insulin did not improve the progression of renal fibrosis and the activation of TGF-beta(1) and Shh signalling. In conclusion, diabetes promotes CKD progression of AKI via activation of the TGF-beta(1) and Shh signalling pathways, but insulin treatment was not enough for preventing the progression of renal fibrosis.

引用

页数：13

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