Saiya Zhu
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Saiya Zhu has a total of 8 co-authors. Here are the top co-authors by number of shared publications:
- Annet Kirabo
Vanderbilt University Medical Center
1 shared publication - Chen Yu
Department of Nephrology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
1 shared publication - Haichun Yang
Vanderbilt University Medical Center 37232 Nashville TN USA
1 shared publication - Jianyong Zhong
Department of Pediatrics and
1 shared publication - Jing Liu
Department of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Putuo District, Shanghai, China
1 shared publication - Valentina Kon
Department of Pediatrics, Division of Pediatric Nephrology, Vanderbilt University Medical Center, Nashville, USA
1 shared publication
Latest Publications
- Open Access
- 22 January 2026
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 11 (5)
LYVE1 ectodomain shedding blunts lymphatic transmigration and clearance of macrophages during kidney injury
Although renal fibrosis is predominantly driven by the accumulated inflammatory cells that secrete proinflammatory factors within the kidney, the key mechanisms underlying macrophage clearance from the kidney are not well understood. The interaction of hyaluronan with lymphatic endothelial hyaluronan receptor 1 (LYVE1) constitutes a critical initial step in macrophage adhesion and removal by lymphatic vessels. This study investigates alterations in LYVE1 during kidney disease and elucidates its role in macrophage trafficking. Three renal fibrosis models demonstrated a reduction in full-length LYVE1 and an increase in the soluble LYVE1 fragment. Immunostaining of fibrotic kidneys showed significantly reduced expression of soluble LYVE1 compared with the intracellular fragment (Cyto-LYVE1), demonstrating ectodomain shedding of LYVE1 in vivo and in vitro. Functionally, human lymphatic endothelial cells exposed to TGF-β1 exhibited a significant decrease in macrophage adhesion and transendothelial migration compared with controls. Mechanistic analyses identified increased matrix metalloproteinase 9 (MMP9) in renal injury as a key upstream regulator of LYVE1 shedding. MMP9 inhibitors reduced LYVE1 shedding, enhanced macrophage adhesion and trafficking, and mitigated macrophage accumulation and disease progression. In conclusion, MMP9-induced LYVE1 shedding is linked to progressive kidney fibrosis and macrophage accumulation. LYVE1 shedding inhibitors offer potential as therapeutic agents for mitigating immune overload and kidney fibrosis.
- 22 January 2026
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 11 (5)
Open AccessLYVE1 ectodomain shedding blunts lymphatic transmigration and clearance of macrophages during kidney injury
Although renal fibrosis is predominantly driven by the accumulated inflammatory cells that secrete proinflammatory factors within the kidney, the key mechanisms underlying macrophage clearance from the kidney are not well understood. The interaction of hyaluronan with lymphatic endothelial hyaluronan receptor 1 (LYVE1) constitutes a critical initial step in macrophage adhesion and removal by lymphatic vessels. This study investigates alterations in LYVE1 during kidney disease and elucidates its role in macrophage trafficking. Three renal fibrosis models demonstrated a reduction in full-length LYVE1 and an increase in the soluble LYVE1 fragment. Immunostaining of fibrotic kidneys showed significantly reduced expression of soluble LYVE1 compared with the intracellular fragment (Cyto-LYVE1), demonstrating ectodomain shedding of LYVE1 in vivo and in vitro. Functionally, human lymphatic endothelial cells exposed to TGF-β1 exhibited a significant decrease in macrophage adhesion and transendothelial migration compared with controls. Mechanistic analyses identified increased matrix metalloproteinase 9 (MMP9) in renal injury as a key upstream regulator of LYVE1 shedding. MMP9 inhibitors reduced LYVE1 shedding, enhanced macrophage adhesion and trafficking, and mitigated macrophage accumulation and disease progression. In conclusion, MMP9-induced LYVE1 shedding is linked to progressive kidney fibrosis and macrophage accumulation. LYVE1 shedding inhibitors offer potential as therapeutic agents for mitigating immune overload and kidney fibrosis.