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Int J Mol Sci. 2016 Nov 8;17(11). pii: E1853.

Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation.

Jagadapillai R1, Rane MJ2,3, Lin X4,5, Roberts AM6,7, Hoyle GW8, Cai L9,10,11, Gozal E12,13,14.

Author information

1
Department of Pediatrics, School of Medicine, University of Louisville, Louisville, KY 40292, USA. rekha.jagadapillai@louisville.edu.
2
Medicine/Nephrology, School of Medicine, University of Louisville, Louisville, KY 40292, USA. madhavi.rane@louisville.edu.
3
Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, KY 40292, USA. madhavi.rane@louisville.edu.
4
Department of Pediatrics, School of Medicine, University of Louisville, Louisville, KY 40292, USA. 15943075920@163.com.
5
Department of Thoracic Surgery, the First Hospital of Jilin University, Changchun 130021, China. 15943075920@163.com.
6
Department of Pediatrics, School of Medicine, University of Louisville, Louisville, KY 40292, USA. andrew.roberts@louisville.edu.
7
Physiology, School of Medicine, University of Louisville, Louisville, KY 40292, USA. andrew.roberts@louisville.edu.
8
Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY 40292, USA. gary.hoyle@louisville.edu.
9
Department of Pediatrics, School of Medicine, University of Louisville, Louisville, KY 40292, USA. lu.cai@louisville.edu.
10
Pharmacology & Toxicology, School of Medicine, University of Louisville, Louisville, KY 40292, USA. lu.cai@louisville.edu.
11
Radiation Oncology, School of Medicine, University of Louisville, Louisville, KY 40292, USA. lu.cai@louisville.edu.
12
Department of Pediatrics, School of Medicine, University of Louisville, Louisville, KY 40292, USA. evelyne.gozal@louisville.edu.
13
Physiology, School of Medicine, University of Louisville, Louisville, KY 40292, USA. evelyne.gozal@louisville.edu.
14
Pharmacology & Toxicology, School of Medicine, University of Louisville, Louisville, KY 40292, USA. evelyne.gozal@louisville.edu.

Abstract

Diabetes is strongly associated with systemic inflammation and oxidative stress, but its effect on pulmonary vascular disease and lung function has often been disregarded. Several studies identified restrictive lung disease and fibrotic changes in diabetic patients and in animal models of diabetes. While microvascular dysfunction is a well-known complication of diabetes, the mechanisms leading to diabetes-induced lung injury have largely been disregarded. We described the potential involvement of diabetes-induced platelet-endothelial interactions in perpetuating vascular inflammation and oxidative injury leading to fibrotic changes in the lung. Changes in nitric oxide synthase (NOS) activation and decreased NO bioavailability in the diabetic lung increase platelet activation and vascular injury and may account for platelet hyperreactivity reported in diabetic patients. Additionally, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway has been reported to mediate pancreatic islet damage, and is implicated in the onset of diabetes, inflammation and vascular injury. Many growth factors and diabetes-induced agonists act via the JAK/STAT pathway. Other studies reported the contribution of the JAK/STAT pathway to the regulation of the pulmonary fibrotic process but the role of this pathway in the development of diabetic lung fibrosis has not been considered. These observations may open new therapeutic perspectives for modulating multiple pathways to mitigate diabetes onset or its pulmonary consequences.

KEYWORDS:

JAK/STAT; endothelial injury; lung fibrosis; nitric oxide; platelet

PMID:
27834824
PMCID:
PMC5133853
DOI:
10.3390/ijms17111853
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the review, and in the decision to publish any results.

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