Open AccessNovel Role of Lck in Leptin-Induced Inflammation and Implications for Renal Aging
Author(s) -
Dae Hyun Kim,
June Whoun Park,
Hyoung Oh Jeong,
Bonggi Lee,
Ki Wung Chung,
Yujeong Lee,
Hyun Ah Jung,
Min Kyung Hyun,
A Kyoung Lee,
Byeong Moo Kim,
Byung Pal Yu,
Hae Young Chung
Publication year - 2019
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2019.0218
Subject(s) - leptin , inflammation , leptin receptor , medicine , proinflammatory cytokine , tyrosine kinase , gene knockdown , stat3 , endocrinology , cancer research , signal transduction , microbiology and biotechnology , biology , receptor , obesity , cell culture , genetics
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.