Key result
Glomerular LRG1 expression rises alongside abnormal angiogenesis and precedes VEGF elevation in diabetic mice.
Why the study?
The pathophysiology of leucine-rich α-2-glycoprotein-1 (LRG1) in diabetic nephropathy remains largely unknown despite its role as a novel proangiogenic factor.
LRG1 modulation should not yet inform diabetic nephropathy care; leaves open its therapeutic relevance pending human studies.
Abnormal angiogenesis plays a major role in the development of early stage diabetic nephropathy. Vascular endothelial growth factor (VEGF) is a classical proangiogenic factor that regulates abnormal glomerular angiogenesis linked to glomerular hypertrophy in the early stage of diabetic nephropathy. Leucine-rich α-2-glycoprotein-1 (LRG1) was recently reported as a novel proangiogenic factor that is expressed in endothelial cells and promotes angiogenesis by modulating the transforming growth factor-β signaling pathway. However, the pathophysiology of LRG1 in diabetic nephropathy remains largely unknown. In the present study, we investigated intrarenal expression of the novel proangiogenic factor LRG1 in diabetic db/db mice by immunohistochemistry and a laser capture microdissection method during the development of diabetic nephropathy. We hypothesized that glomerular LRG1 expression is increased earlier than VEGF expression under conditions of pathological angiogenesis in the early stage of diabetic nephropathy. Thus, we compared glomerular expression of VEGF and LRG1 in diabetic db/db mice at 16 and 24 weeks of age. At 16 weeks, diabetic db/db mice exhibited glomerular hypertrophy with abnormal angiogenesis characterized by endothelial cell proliferation, which was concomitant with an increase in LRG1 expression of glomerular endothelial cells. However, glomerular VEGF expression was not increased at this early stage. At 24 weeks, the features of early diabetic nephropathy in db/db mice had developed further, along with further enhanced glomerular LRG1 expression. At this late stage, glomerular VEGF and fibrosis-related-gene expression was also significantly increased compared with nondiabetic db/m mice. These results suggest that LRG1 plays a pivotal role in the initial development of diabetic nephropathy by promoting abnormal angiogenesis, thereby suggesting that LRG1 is a potential preemptive therapeutic target of diabetic nephropathy.
No takes yet. Share an insight, caveat, or question.
Haku et al. (2018) studied Diabetic nephropathy. Diabetic condition (db/db mice) vs. Nondiabetic db/m mice was evaluated on Glomerular expression of VEGF and LRG1. In diabetic db/db mice, glomerular LRG1 expression increased at 16 weeks alongside abnormal angiogenesis, preceding the increase in VEGF expression which occurred at 24 weeks.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: