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- Title
Novel Role of Lck in Leptin-Induced Inflammation and Implications for Renal Aging.
- Authors
Dae Hyun Kim; June Whoun Park; Hyoung Oh Jeong; Bonggi Lee; Ki Wung Chung; Yujeong Lee; Hee Jin Jung; Min Kyung Hyun; A. Kyoung Lee; Byeong Moo Kim; Byung Pal Yu; Hae Young Chung
- 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.
- Subjects
LEPTIN; INFLAMMATION
- Publication
Aging & Disease, 2019, Vol 10, Issue 6, p1174
- ISSN
2152-5250
- Publication type
Article
- DOI
10.14336/AD.2019.0218