Salvianolic acid B attenuates renal interstitial fibrosis by regulating the HPSE/SDC1 axis
MOLECULAR MEDICINE REPORTS
Authors: Hu, Yang; Wang, Man; Pan, Yunzheng; Li, Qingju; Xu, Li
Abstract
Salvianolic acid B (Sal B) is one of the main water-soluble components of Salvia miltiorrhiza Bge. Numerous reports have demonstrated that it could exert significant renal-protective effects, but the underlying mechanism remains unclear. The present study demonstrated that Sal B could alleviate renal injury by regulating the heparanase/syndecan-1 (HPSE/SDC1) axis. In vivo, the serum creatinine, blood urea nitrogen, transforming growth factor-beta 1 (TGF-beta 1) and fibroblast growth factor-2 (FGF-2) levels, and the histopathological changes of mice kidneys were examined. Sal B could notably reduce the renal injury caused by left ureteral ligation. In vitro, Sal B downregulated the expression levels of HPSE/FGF-2/TGF-beta 1/alpha -smooth muscle actin and upregulated the expression levels of SDC1/E-cadherin in angiotensin II-stimulated HK-2 cells in a dose-dependent manner. In summary, to the best of the authors' knowledge, the present study provided evidence for the first time that Sal B could exert renal-protective effects via the inhibition of the HPSE/SDC1 axis, and these results suggest that the administration of Sal B may be a novel therapeutic strategy in treating renal interstitial fibrosis.
Association of heparan sulfate proteoglycans SDC1 and SDC4 polymorphisms with breast cancer in an Australian Caucasian population
TUMOR BIOLOGY
Authors: Okolicsanyi, Rachel K.; Buffiere, Anne; Jacinto, Jose M. E.; Chacon-Cortes, Diego; Chambers, Suzanne K.; Youl, Philippa H.; Haupt, Larisa M.; Griffiths, Lyn R.
Abstract
Breast cancer is a common disease in both developing and developed countries with early identification and treatment improving prognosis and survival. Heparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix (ECM) that mediate cell adhesion, motility, proliferation, invasion and cell signalling. Members of the syndecan family of HSPGs have been identified to be involved in breast cancer progression through their varied interactions with a number of growth factors, ligands and receptors. Specifically, high expression levels of syndecan-1 (SDC1) have been demonstrated in more invasive breast tumours while elevated syndecan-4 (SDC4) levels have been identified to correspond with improved prognosis. With genetic changes in the syndecans and their association with breast cancers plausible, we examined two single nucleotide polymorphisms in SDC1 (rs1131351) and SDC4 (rs67068737) within an Australian Caucasian breast cancer case/control population. No association was found with SDC4 and breast cancer in our population. However, a significant association between SDC1 and breast cancer was identified in both our case/control population and in a replication cohort. When both populations were combined for analysis, this association became more significant (genotype, p = 0.0003; allele, p = 0.0001). This data suggests an increased risk of developing breast cancer associated with the presence of the C allele of the SDC1 rs1131351 single nucleotide polymorphism (SNP) and may provide a marker toward early breast cancer detection.