Abstract
Proteinuria is an important cause of progressive tubulo-interstitial damage. Whether proteinuria could trigger a renal lymphangiogenic response has not been established. Moreover, the temporal relationship between development of fibrosis, inflammation and lymphangiogenesis in chronic progressive kidney disease is not clear yet. Therefore, we evaluated the time course of lymph vessel (LV) formation in relation to proteinuria and interstitial damage in a rat model of chronic unilateral adriamycin nephrosis. Proteinuria and kidneys were evaluated up to 30 weeks after induction of nephrosis. LVs were identified by podoplanin/VEGFR3 double staining. After 6 weeks proteinuria was well-established, without influx of interstitial macrophages and myofibroblasts, collagen deposition, osteopontin expression (tubular activation) or LV formation. At 12 weeks, a ∼3-fold increase in cortical LV density was found (p<0.001), gradually increasing over time. This corresponded with a significant increase in tubular osteopontin expression (p<0.01) and interstitial myofibroblast numbers (p<0.05), whereas collagen deposition and macrophage numbers were not yet increased. VEGF-C was mostly expressed by tubular cells rather than interstitial cells. Cultured tubular cells stimulated with FCS showed a dose-dependent increase in mRNA and protein expression of VEGF-C which was not observed by human albumin stimulation. We conclude that chronic proteinuria provoked lymphangiogenesis in temporal conjunction with tubular osteopontin expression and influx of myofibroblasts, that preceded interstitial fibrosis.
Highlights
Proteinuria is a noticeable risk factor for development of chronic kidney disease (CKD) and its reduction has renoprotective effects, slowing down progression to end-stage renal disease (ESRD) [1,2,3]
Since many kidneys had Focal glomerulosclerosis (FGS) score of zero, the Clinical Parameters Proteinuria was significantly increased in adriamycin-injected rats, compared to saline-injected controls
In this report we show in a unilateral adriamycin model in the rat that early, established, proteinuria is not associated with lymphangiogenesis
Summary
Proteinuria is a noticeable risk factor for development of chronic kidney disease (CKD) and its reduction has renoprotective effects, slowing down progression to end-stage renal disease (ESRD) [1,2,3]. Proteinuria is a marker of renal failure progression, but is directly involved in the pathogenesis of tubulointerstitial fibrosis in the kidney as well [4]. The extent of proteinuriainduced tubulointerstitial changes limits the efficacy of antiproteinuric and renoprotective treatment with renin–angiotensin system (RAS) blockers [13], even when the changes are still within the pro-fibrotic range, highlighting the importance of tubulointerstitial damages in response to therapy in proteinuric patients. This warrants better exploration of the (pro-)fibrotic response to proteinuria
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
