Ledviny a lymfatický systém
Ledviny
- Ring-like anastomosis in the renal hilum, from which lymphatic vessels originated
- These vessels branched and increased in length over the course of renal development [37]
- Ring-like lymphatic anastomosis resided under the nascent renal pelvis, identified by the urothelial marker UPK3A [37]
- Rapid expansion of the lymphatic plexus
- Could be driven by the accumulation of interstitial fluid, which has extravasated from the renal vasculature and stimulates lymphatic expansion [37]
- One critical paracrine factor is vascular endothelial growth factor C (VEGF-C),
- Binds to VEGFR-3
- Promotes the sprouting and migration of lymphatic endothelial cells [37]
- Renal hilum; where kidney lymphatics first arise, is a VEGF-C-rich niche [37]
- Lymphatics form by sprouting from veins and pre-existing lymphatics, a process termed lymphangiogenesis
- Assembly of lymphatic progenitors, a process termed lymphvasculogenesis
- May represent a tissue-specific population of lymphatic progenitor cells
- Isolated clusters of lymphatic endothelial cells, as observed during the development of
- Mesenteric, meningeal, dermal and cardiac lymphatic vasculature
- Mouse embryonic kidneys - PROX1+/LYVE-1+ 192 cellular clusters, which were structurally distinct from the lymphatic vessel plexus [37]
- Expression of VEGFR-3 and podoplanin = potvrzení že jde o lymfatické epiteliální buňky [37]
- LYVE-1, VEGFR-3 and podoplanin
- All highlighted filopodia-like processes extending from lymphatic clusters in the kidney
- Likely analogous to the migratory tips that extend from nascent lymphatic endothelium
Renal fibrosis
- That interstitial infiltration of activated leukocytes triggers renal fibrogenesis
- By direct injury of renal parenchymal cells
- By secretion of cytokines that promote myofibroblast activation
- Localized immune system components
- Inflammatory mediators in kidneys [42]
- Lymphatic vessels (LVs) link the kidney to the larger immune system
- Exclusive conduit for passage of
- Soluble antigens
- Immune cells from the kidney to the renal draining lymph nodes (RDLNs) [42]
- Recruiting CCR7+ dendritic ceslls (DCs) and lymphocytes into RDLN and spleen
- Inducing systemic CCR7+ cell recruitment
- Accelerating intrarenal inflammation [42]
- LVs therefore participate in
- Shaping kidney immunity
- Potentially balancing physiological pathways [42]
- CKD patients with higher density intrarenal LVs
- Presented with more severe proteinuria and renal fibrosis and decreased eGFR !!! [42]
- Human renal transplant studies suggested that
- Lymphatic progenitor cells are derived from the circulation
- Then incorporated into growing LVs in kidneys [42]
- “sprout” from the preexisting local lymphatic network with zero or minimal contributions from BM-derived cells [42]
- Lymphangiogenesis following human kidney transplants was associated with immunologically active lymphocytic infiltrates [42]
- Targeting VEGFR3 positively affected renal fibrosis [42]
- Gene responsible for the majority of cases of autosomal dominant (AD)PKD regulate
- Extra-renal lymphatic endothelial cell migration
- Lymphatic vessel morphogenesis [37]
- Oedema and structural defects in lymphatic vasculature have been observed in Pkd1 mutant zebrafish and mice
- Decreased branching
- Increased diameter of dermal lymphatic vessels [37]
- Increased the abundance of lymphatics within the kidney
- Reduced disease severity in two mouse models of PKD21 [37]
- Presented with subcutaneous oedema [37]
- Corticomedullary cysts lined by tubular epithelial cells in kidenys
- Cysts were in close proximity to cortical lymphatic vessels
- Excess tissue fluid in PKD may be able to enter lymphatic vessels via paracellular transport
- There might be direct or indirect molecular interactions between cyst epithelium and lymphatic endothelial cells [37]
- Significant reduction by 18% in the mean diameter of the largest lymphatic vessel in Pkd1RC/RC kidneys compared to Pkd1+/+ 296 controls
- no significant differences between homozygous mutants and wildtype controls were observed in the:
- Total number of vessel branches
- Range of vessel branch lengths
- Total volume of the lymphatic network [37]
- Inadequate clearance of tissue fluid by lymphatic vessels may contribute to the expansion of cysts in PKD [37]
