Pleiotropic effects of hepatocyte growth factor in proximal tubule involve different signaling pathways

Pleiotropic effects of hepatocyte growth factor in proximal tubule involve different signaling pathways. Hepatocyte growth factor (HGF) accelerates renal tubule cell regeneration and induces tubulogenic differentiation via the intracellular tyrosine kinase (TK) domain of its receptor, the proto-oncogene c-Met. We tested whether different signaling pathways may be involved by examining HGF binding and effects on cell proliferation, migration, scattering, and tubulogenic differentiation in the bipolar differentiating rabbit proximal tubule cell line PT-1 under serum-free conditions in the presence or absence of the protein TK inhibitors (PTKIs) herbimycin-A, genistein, methyl-2,5-dihydroxycinnamate, and geldanamycin. These PTKIs inhibit pp60c-src, a nonreceptor TK involved in cell-growth control. HGF bound to a single high-affinity receptor class, increased microvilli numbers 1.5-fold, enhanced cell proliferation and migration 1.8-fold, and stimulated formation of tubule structures 2.2-fold. PTKI inhibited the mitogenic and motogenic effects of HGF with different potencies and comparable maximal effects but had no specific influence on HGF-induced tubulogenic cell differentiation. These data underline the importance of pp60c-src in mediating mitogenic and motogenic effects of HGF, whereas stimulation of tubulogenic cell differentiation may be transduced by a pp60c-src–independent pathway

Scotland’s Biodiversity Progress to 2020 Aichi targets: Aichi target 13 - Genetic Diversity Maintained - Supplementary Report 2020

As there is no agreed national list of species of socio-economic and/or cultural value for Scotland, we developed a set of criteria for selecting species. These include: • Species prioritised for conservation value • Species identified as being culturally important • Species providing important ecosystem services • Game species • Species collected for food or medicine Using these criteria, we selected 26 species for initial assessment. For each species, we produced a Genetic Scorecard, outlining: • Relevant genetic conservation issues for the species in question • The importance of its genetic diversity on an international scale • An evaluation of the genetic risks facing in situ populations • A statement of confidence in the assessment • The degree to which representation in ex situ collections mitigate against genetic diversity loss. • An overall ‘traffic light’ score of genetic risks and whether current conservation actions are effective Using 2010 as a baseline reference point, the approach assesses contemporary genetic issues, and likely future issues during a 25-year window from the point of assessment. For quantification of levels of risk, we adopted the following framework: • Negligible: No obviously detectable genetic problems occurring or expected over the next 25 years. • Moderate: Moderate genetic problems occurring or expected over the next 25 years; e.g.: - Moderate loss of populations that are likely to contain unique diversity (e.g., resulting in losses of up to 25% of important genetic types / distinct populations); - Clearly observable fitness problems in up to 25% of populations due to low genetic variation and subsequent inbreeding depression; - Marked and clearly observable loss of genetic integrity by hybridisation at up to 25% of populations; - Severe restrictions on regeneration/recruitment/reproduction in many or most populations of long-lived species limiting evolutionary change in the immediate future. • Serious: Serious genetic problems occurring or expected over the next 25 years; e.g.: - Severe loss of populations that are likely to contain unique diversity (e.g., resulting in losses of > 25% of important genetic types / distinct populations); - Loss of any highly divergent endemic lineages that are globally unique; - Strong, clearly observable fitness problems in >25% of populations due to low genetic variation and subsequent inbreeding depression; - Marked and clearly observable loss of genetic integrity by hybridisation at >25% of populations. The assessment is based on expert opinion, using direct genetic data, where available, combined with information on species biology, abundance and distribution. Where no direct genetic data are available, the genetic risk assessment is based on species biology, abundance and distribution