TRKA AND TRKC EXPRESSION IS INCREASED IN HUMAN DIABETIC SKIN

Nerve growth factor (NGF) is reduced in epidermal keratinocytes in hum an diabetic skin, and this decrease has been related to dysfunction of cutaneous sensory fibres. In vitro studies show that keratinocytes ex press both NGF and its high-affinity receptor, trkA, and that NGF may increase keratinocyte proliferation and its own expression via an auto crine loop. However, the level of trkA expression in vivo by keratinoc ytes in normal and diabetic skin is unknown. We have therefore measure d trkA expression in calf skin biopsies from patients with early subcl inical diabetic neuropathy and control subjects, using in situ hybridi sation combined with image analysis quantification. Expression of trkC was also studied, as its endogenous ligand neurotrophin-3 (NT-3) is r elated to NGF, and is present in human epidermis. Hybridisation signal was seen for both trkA and trkC localised throughout the epidermal la yer of control skin, with a higher density of silver grain deposition observed for trkA mRNA. However, in diabetic epidermis there was a sig nificant increase (P < 0.001) for both trk A (control, 0.178 +/- 0.013 ; diabetic, 0.304 +/- 0.032; mean silver grain counts/mu m(2) +/-SEM) and trkC expression (controls, 0.059 +/- 0.004; diabetics, 0.191 +/- 0 .010). The up-regulation of epidermal trk receptors may result from de creased autocrine neurotrophin action, and could represent a compensat ory mechanism. (C) 1997 Elsevier Science Ireland Ltd.