Lieberthal W, McKenney J B, Kiefer C R, Snyder L M, Kroshian V M, Sjaastad M D
Renal Section, Boston University Medical Center Hospital, MA 02118, USA.
J Am Soc Nephrol. 1997 Feb;8(2):175-83. doi: 10.1681/ASN.V82175.
beta 1 integrin-mediated adhesion between renal tubular cells after anoxic injury. This study examined the effect of sublethal injury, induced by ATP depletion (5 mM cyanide in the absence of dextrose), on the distribution and function of beta 1 integrins in primary cultures of mouse proximal tubular (MPT) cells. It was shown in this study that sublethal injury results in loss of focal contacts present in uninjured MPT cells, and that the beta 1 integrin molecule becomes redistributed to the apical membrane domain of sublethally injured cells. Polystyrene beads coated with Arg-Gly-Asp (RGD)-containing peptide adhere to the surface of sublethally injured MPT cells but not to control, dextrose-treated cells, indicating that the beta 1 integrins present on the apical surface of the cell remain functional. The presence of an excess of free RGD-containing peptide reduces binding of RGD-coated beads to sublethally injured MPT cells by approximately 50%. It was also demonstrated that adherence of MPT cells in suspension to cyanide-treated monolayers is increased more than 300% above adhesion to control, uninjured monolayers. This abnormal cell-cell adhesion is ameliorated by the presence of an excess of RGD-containing peptide and is reversed if cyanide-treated cells are allowed to recover for 1 h. It was concluded that the beta 1 integrin becomes expressed on the apical surface of MPT cells after sublethal injury. These apically expressed integrins remain functional and mediate aberrant adhesion between MPT cells.
β1整合素介导缺氧损伤后肾小管细胞之间的黏附。本研究检测了由ATP耗竭(在无葡萄糖的情况下加入5 mM氰化物)诱导的亚致死性损伤对小鼠近端肾小管(MPT)细胞原代培养物中β1整合素分布和功能的影响。本研究表明,亚致死性损伤导致未损伤的MPT细胞中焦点黏附丧失,并且β1整合素分子重新分布到亚致死性损伤细胞的顶端膜结构域。包被含精氨酸 - 甘氨酸 - 天冬氨酸(RGD)肽的聚苯乙烯珠可黏附于亚致死性损伤的MPT细胞表面,但不黏附于对照的、葡萄糖处理的细胞,这表明细胞顶端表面存在的β1整合素仍具有功能。过量游离含RGD肽的存在使RGD包被的珠与亚致死性损伤的MPT细胞的结合减少约50%。还证明,悬浮的MPT细胞与氰化物处理的单层细胞的黏附比与对照的、未损伤的单层细胞的黏附增加了300%以上。这种异常的细胞间黏附可通过过量含RGD肽的存在而改善,如果氰化物处理的细胞恢复1小时则可逆转。得出的结论是,亚致死性损伤后β1整合素在MPT细胞的顶端表面表达。这些顶端表达的整合素仍具有功能,并介导MPT细胞之间的异常黏附。