Peruzzi L, Amore A, Cirina P, Trusolino L, Basso G, Ricotti E, Emancipator S N, Marchisio P C, Coppo R
Nephrology and Dialysis Department, Regina Margherita Children's Hospital, Torino, Italy.
Kidney Int. 2000 Dec;58(6):2331-40. doi: 10.1046/j.1523-1755.2000.00417.x.
Signal transduction by mesangial cell (MC) integrins regulates cell growth and survival, extracellular matrix production, and organization. The aim of the study was to investigate human MC integrin modulation by differently glycosylated IgA and macromolecular IgA, which are thought to play a pathogenetic role in IgA nephropathy (IgAN).
MCs were incubated with purified human polymeric IgA, heat-aggregated IgA, IgA glycoforms generated by enzymatic hydrolysis of saccharide residues and serum fractions from IgAN patients, and controls isolated by lectin affinity and containing IgA with peculiar glycan patterns. Integrins were quantitated by flow cytometry.
Cultured MCs highly expressed alphavbeta3 and some alpha3beta1; alphavbeta3 was up-regulated by matrix components (P < 0.02). In vitro desialylated and degalactosylated polymeric human IgA enhanced alphavbeta3 expression on cultured MCs (P < 0.001). Serum IgA glycoforms isolated from IgAN patients with high exposure of internal sugars, GalNAc, Neu5Ac2,6GalNAc, and Man enhanced alphav expression on cultured MCs more than healthy controls. CONCLUSIONS.: These data support the hypothesis that IgA glycation plays a role in modulating the cell-matrix interaction, and that this mechanism can be operating in IgAN.
系膜细胞（MC）整合素介导的信号转导可调节细胞生长与存活、细胞外基质的产生及组织化。本研究旨在探究不同糖基化的IgA和大分子IgA对人MC整合素的调节作用，这些物质被认为在IgA肾病（IgAN）的发病机制中起作用。
将MC与纯化的人聚合IgA、热聚集IgA、通过糖类残基酶解产生的IgA糖型、IgAN患者的血清组分以及通过凝集素亲和分离得到的含有特定聚糖模式IgA的对照物一起孵育。通过流式细胞术对整合素进行定量分析。
培养的MC高表达αvβ3和一些α3β1；αvβ3被基质成分上调（P < 0.02）。体外去唾液酸化和去半乳糖基化的人聚合IgA可增强培养的MC上αvβ3的表达（P < 0.001）。从具有高内部糖暴露（GalNAc、Neu5Ac2,6GalNAc和Man）的IgAN患者中分离出的血清IgA糖型比健康对照更能增强培养的MC上αv的表达。结论：这些数据支持以下假设，即IgA糖基化在调节细胞-基质相互作用中起作用，并且这种机制可能在IgAN中起作用。
