Translational research : the journal of laboratory and clinical medicine
-
Homozygosity for the hemoglobin (Hb) S mutation (HbSS, sickle cell anemia) results in hemoglobin polymerization under hypoxic conditions leading to vaso-occlusion and hemolysis. Sickle cell anemia affects 1:500 African Americans and is a strong risk factor for kidney disease, although the mechanisms are not well understood. Heterozygous inheritance (HbAS; sickle cell trait) affects 1:10 African Americans and is associated with an increased risk for kidney disease in some reports. ⋯ Gene expression studies highlighted the differential expression of several genes involved in prostaglandin metabolism (AKR1C18), heme and iron metabolism (HbA-A2, HMOX1, SCL25A37), electrolyte balance (SLC4A1, AQP6), immunity (RSAD2, C3, UBE2O), fatty acid metabolism (FASN), hypoxia hall-mark genes (GCK, SDC3, VEGFA, ETS1, CP, BCL2), as well as genes implicated in other forms of kidney disease (PODXL, ELMO1, FRMD3, MYH9, APOA1). Pathway analysis highlighted increased gene enrichment in focal adhesion, extracellular matrix-receptor interaction, and axon guidance pathways. In summary, using transgenic sickle mice, we observed that inheritance of the HbS mutation is associated with glomerular and tubular damage and identified several candidate genes and pathways for future investigation in sickle cell trait and sickle cell anemia-related kidney disease.
-
Nuclear factor-κB (NF-κB) has been widely implicated in the development and progression of cancer. In colorectal cancer (CRC), NF-κB has a key role in cancer-related processes such as cell proliferation, apoptosis, angiogenesis, and metastasis. ⋯ Although there is sufficient evidence gained from cell lines and animal models that NF-κB is involved in cancer-related processes, because of a lack of studies in human tissue, the clinical evidence of its importance is limited in patients with CRC. This review summarizes evidence relating to how NF-κB is involved in the development and progression of CRC and comments on future work to be carried out.