Transgender in Africa: invisible, inaccessible, or ignored?

Transgender people are an important key population for HIV risk globally, and several studies have found HIV prevalence rates in transgender populations that are significantly higher than those among other key populations such as men who have sex with men (MSM). There is a lack of research on transgender populations in Africa, and at present, there is almost no data available on HIV prevalence and risk among transgender people on the continent. It is possible that the invisibility of transgender people in epidemiological data from Africa is related to the criminalisation of same-sex behaviour in many countries and the subsequent fear of negative repercussions from participation in research. Alternatively, transgender people may be being overlooked in research due to confusion among researchers about how to ask questions about gender identity. It is also possible that transgender populations have simply been ignored in research to date. Without research on transgender-specific HIV prevalence and risk, it is very difficult to know what interventions and services are needed for this risk population. Therefore, it is important that researchers, governments, Non Governmental Organisations (NGOs) and donor organisations begin to pay explicit attention to transgender people in their HIV-related research and programmes in Africa.

c-Met responsiveness of isolated hepatocytes evaluated in an in vitro de-differentiation model.

Hepatocyte growth factor (HGF) accelerates tissue regeneration and ameliorates tissue fibrosis through its ligand c-Met receptor tyrosine kinase. Hence, HGF is currently discussed as an attractive therapeutic candidate for fatal liver diseases. However, it remains unclear whether c-Met of de-differentiated hepatocytes adequately responds to HGF in an impaired liver. Therefore, we investigated c-Met expression and c-Met responsiveness to HGF in an experimental de-differentiation cell culture system. Primary rat hepatocytes were seeded on a two-dimensional collagen matrix or embedded within a three dimensional collagen gel to guarantee intact cell geometry. Cells were cultivated in a growth factor enriched extracellular milieu (de-differentiation medium), or in a chemically defined differentiation medium, representing physiologically intact hepatocytes. c-Met surface expression was determined by flow cytometry. Receptor localisation was examined by confocal microscopy, c-Met and phosphorylated c-Met protein were determined by western blotting. Hepatocyte-specific asialoglycoprotein receptor (ASGPr) was examined to control the differentiation status of the cells. Growth factor enriched milieu induced a rapid loss of ASGPr with a significant increase of c-Met surface level and a decrease in c-Met protein level. Surprisingly, the increased amount of c-Met surface expression was associated with its loss of responsiveness to HGF. The addition of bile acids into the culture medium had significantly delayed the process of de-differentiation and restrained the drastic elevation of c-Met (tauroursodeoxycholic acid > ursodeoxycholic acid). Application of the three-dimensional hepatocellular architecture stabilized the c-Met surface receptor level and rendered c-Met activation. We have demonstrated that growth factor enriched extracellular milieu and loss of intact liver architecture seems to be accompanied by an up-regulation of c-Met surface level. Our findings suggest that irresponsiveness of c-Met to soluble HGF was possibly caused by an excessive HGF production and receptor over-stimulation. Both events should be considered when establishing an HGF-based therapy for fibrosis/cirrhosis.