Format

Send to

Choose Destination
JCI Insight. 2018 Sep 20;3(18). pii: 99592. doi: 10.1172/jci.insight.99592. eCollection 2018 Sep 20.

Beclin-1 regulates cigarette smoke-induced kidney injury in a murine model of chronic obstructive pulmonary disease.

Author information

1
Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
2
NewYork-Presbyterian Hospital, Weill Cornell Medicine, New York, New York, USA.
3
Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
4
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Chronic obstructive pulmonary disease (COPD), associated with cigarette smoke-induced (CS-induced) emphysema, contributes significantly to the global health care burden of disease. Although chronic kidney disease (CKD) may occur in patients with COPD, the relationship between COPD and CKD remains unclear. Using a murine model of experimental COPD, we show that chronic CS exposure resulted in marked kidney injury and fibrosis, as evidenced by histological and ultrastructural changes, altered macrophage subpopulations, and expression of tissue injury, fibrosis, and oxidative stress markers. CS induced mitochondrial dysfunction, and increased autophagic flux in kidney tissues and in kidney tubular epithelial (HK-2) cells, as determined by LC3B turnover assays. Mice heterozygous for Beclin-1 (Becn1+/-) were protected from the development of kidney tissue injury and renal fibrosis in response to CS exposure, and displayed impaired basal and inducible mitochondrial turnover by mitophagy. Interestingly, CS caused a reduction of Beclin-1 expression in mouse kidneys and kidney tubular epithelial cells, attributed to increased autophagy-dependent turnover of Beclin-1. These results suggest that Beclin-1 is required for CS-induced kidney injury and that reduced levels of Beclin-1 may confer renoprotection. These results identify the kidney as a target for CS-induced injury in COPD and the Beclin-1-dependent autophagy pathway as a potential therapeutic target in CKD.

KEYWORDS:

Autophagy; COPD; Chronic kidney disease; Nephrology; Pulmonology

PMID:
30232271
PMCID:
PMC6237223
DOI:
10.1172/jci.insight.99592
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center