Insulin-like growth factor signalling and its significance as a biomarker in fish and shellfish research

Regression of the rat ventral prostate occurs when the level of 5α-dihydrotestosterone, the trophic hormone, drops below the threshold required to suppress apoptosis. The induction of apoptosis in the ventral prostate is accompanied by the increase in the steady-state level of a number of mRNAs coding for proteins that are involved in the latter stages of apoptosis and thus represent secondary thanatogens. These include proteases (cathepsins, plasminogen activators, and collagenase), clusterin, poly(ADP)ribose polymerase, tenascin, and several unidentified genes, as well as several RNases and the classical Ca2+,Mg2+-dependent endonuclease. In addition, insulin-like growth-factor-binding protein 5 (IGFBP-5) is induced de novo. We propose that IGFBP-5 may serve to trigger the apoptotic process through the attenuation of the insulin-like growth factor signalling system (which is necessary for cell survival), and as such, represents a primary thanatogen in the prostate.Key words: insulin-like growth factor, insulin-like growth-factor-binding proteins, prostate, apoptosis, regression, gene expression.

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Pseudomonas aeruginosa lectin LecB impairs keratinocyte fitness by abrogating growth factor signalling

Life Science Alliance ◽

10.26508/lsa.201900422 ◽

2019 ◽

Vol 2 (6) ◽

pp. e201900422 ◽

Cited By ~ 1

Author(s):

Alessia Landi ◽

Muriel Mari ◽

Svenja Kleiser ◽

Tobias Wolf ◽

Christine Gretzmeier ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Growth Factor ◽

Tissue Repair ◽

Human Keratinocytes ◽

Receptor Activation ◽

Membrane Receptors ◽

Insulin Like Growth Factor ◽

Keratinocyte Proliferation ◽

Growth Factor Signalling ◽

Binding Lectin

Lectins are glycan-binding proteins with no catalytic activity and ubiquitously expressed in nature. Numerous bacteria use lectins to efficiently bind to epithelia, thus facilitating tissue colonisation. Wounded skin is one of the preferred niches for Pseudomonas aeruginosa, which has developed diverse strategies to impair tissue repair processes and promote infection. Here, we analyse the effect of the P. aeruginosa fucose-binding lectin LecB on human keratinocytes and demonstrate that it triggers events in the host, upon binding to fucosylated residues on cell membrane receptors, which extend beyond its role as an adhesion molecule. We found that LecB associates with insulin-like growth factor-1 receptor and dampens its signalling, leading to the arrest of cell cycle. In addition, we describe a novel LecB-triggered mechanism to down-regulate host cell receptors by showing that LecB leads to insulin-like growth factor-1 receptor internalisation and subsequent missorting towards intracellular endosomal compartments, without receptor activation. Overall, these data highlight that LecB is a multitask virulence factor that, through subversion of several host pathways, has a profound impact on keratinocyte proliferation and survival.

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