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CIDEC Gene Silencing Alleviates Pulmonary Vascular Remodeling in a Type 2 Diabetic Rat Model.

CIDEC Gene Silencing Alleviates Pulmonary Vascular Remodeling in a Type 2 Diabetic Rat Model.
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Sui DX, Zhou HM, Wang F, Zhong M, Zhang W, Ti Y,


Sui DX, Zhou HM, Wang F, Zhong M, Zhang W, Ti Y, (click to view)

Sui DX, Zhou HM, Wang F, Zhong M, Zhang W, Ti Y,

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Journal of diabetes investigation 2017 10 27() doi 10.1111/jdi.12768
Abstract
AIMS
CIDEC was proven to be closely associated with the development of insulin resistance and metabolic syndrome. We aimed to investigate whether the CIDEC gene silencing could alleviate pulmonary vascular remodeling in a type 2 diabetic rat model.

MATERIALS AND METHODS
We built a type 2 diabetic rat model. An adenovirus harboring CIDEC small interfering RNA (siRNA) was then injected via the jugular vein to silence the CIDEC gene. After HE and Sirius red staining, we detected indexes of the pulmonary arterioles remodeling. Immunohistochemical staining of PCNA was used to evaluate the pulmonary arterial smooth muscle cell proliferation. Apoptosis was evaluated by TUNEL reaction and Western-blotting. The levels of signaling pathway proteins expression were measured by Western-blotting analyses.

RESULTS
Histological analysis of pulmonary artery showed that the thickness of the adventitia and medial layer increased notably in type 2 diabetic rats. Immunohistochemistry showed that more PCNA positive pulmonary arterial smooth muscle cells could be seen in type 2 diabetic rats, and after CIDEC gene silencing PCNA positive cells decreased accordingly. Cleaved caspase-3 and Cleaved PARP measured by Western-blotting indicated increased apoptosis with overexpressed CIDEC in diabetes. TUNEL reaction showed that the apoptosis mainly occurred in endothelial cells. Western-blotting analysis demonstrated CIDEC overexpression in rats with diabetes, and phosphorylated AMPKα expression was significantly decreased. After CIDEC gene silencing, the expression of phosphorylated AMPKα was up-regulated.

CONCLUSIONS
CIDEC/AMPK signaling pathway could be a potential therapeutic candidate against pulmonary vascular diseases in type 2 diabetes. This article is protected by copyright. All rights reserved.

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