Molecular forms of NGF in human and rat neuropathic tissues: decreased NGF precursor-like immunoreactivity in human diabetic skin.

Autor: Yiangou, Yiangos, Facer, Paul, Sinicropi, Dominick V., Boucher, Tim J., Bennett, David L.H., McMahon, Stephen B., Anand, Praveen
Předmět:
Zdroj: Journal of the Peripheral Nervous System; Sep2002, Vol. 7 Issue 3, p190, 8p
Abstrakt: Precursors of NGF have been shown to be the predominant forms of this neurotrophin in human brain and peripheral tissues, and proNGF has been shown recently to preferentially bind p75[sup NTR] with high affinity. In our studies of human and rat skin and nerve extracts, a 53 kDa band was detected by Western blot using antibodies against rhNGF or prepro-NGF (-91 to -60), that could correspond to a previously described modified prepro-NGF-like molecule. The relative optical intensity of the 53-kDa bands was markedly reduced in skin extracts from patients with subclinical diabetic neuropathy (diabetic: 1.5, 1.0-8.0, n = 6; controls: 52.0, 23.0-85.0, n = 6, p = 0.0022) but was increased in extracts of inflamed colon from patients with Crohn's disease (inflamed: median 12.0, range 0.112.0, n = 11: controls: 0.1, 0.1-3.0, n = 8, p = 0.0055). Antibodies to both rhNGF and prepro-NGF immunostained basal keratinocytes in tissue sections of normal human and rat skin showed accumulation of immunoreactivity in nerve fibers distal to sciatic nerve ligation in rats. Prepro-NGF antibody immunostained rat large/medium sensory neurons, whereas only small sensory neurons were stained with antibodies to mature rhNGF, suggesting that prepro-NGF may be preferentially taken up and transported by p75[sup NTR]. The different molecular forms derived from prepro-NGF are likely to be of importance in sensory mechanisms, and deserve further investigation. [ABSTRACT FROM AUTHOR]
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