Novel Role of Lck in Leptin-Induced Inflammation and Implications for Renal Aging.

Abstract:

:Aging is associated with increased fat mass and elevated serum leptin levels (hyperleptinemia), causing proinflammation in the kidneys where it plays a primary role in the removal of endogenous leptin from the circulation. Lymphocyte-specific kinase (Lck) is a positive regulator of inflammatory signaling and a potential treatment target for age-related diseases, but its role in leptin signaling is unknown. Here, we investigated how Lck influences hyperleptinemia-induced inflammation in kidney tissues from 6- and 21-month-old rats. Results indicate that Lck expression and activation increased significantly in aged rat kidneys, especially at renal tubules. Furthermore, we identified interactions between Lck and short leptin-receptor isoforms, suggesting that Lck is a protein tyrosine kinase regulating leptin signaling. We further investigated whether increased Lck expression in renal tubular epithelial cells and macrophage infiltration are associated with leptin-induced inflammation. We then demonstrated that leptin activates Lck and proinflammatory transcription factors (STAT3 and NF-κB), while Lck knockdown modulates the expression of both transcription factors. Collectively, these data implicate that Lck leads to development of leptin-induced renal inflammation during aging. Inhibition of this protein tyrosine kinase may therefore be an appropriate therapeutic option for protection against age-related hyperleptinemia.

journal_name

Aging Dis

journal_title

Aging and disease

authors

Kim DH,Park JW,Jeong HO,Lee B,Chung KW,Lee Y,Jung HJ,Hyun MK,Lee AK,Kim BM,Yu BP,Chung HY

doi

10.14336/AD.2019.0218

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

1174-1186

issue

6

issn

2152-5250

pii

ad-10-6-1174

journal_volume

10

pub_type

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