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Molecular forms of NGF in human and rat neuropathic tissues: decreased NGF precursor‐like immunoreactivity in human diabetic skin
Author(s) -
Yiangou Yiangos,
Facer Paul,
Sinicropi Dominick V.,
Boucher Tim J.,
Bennett David L.H.,
McMahon Stephen B.,
Anand Praveen
Publication year - 2002
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2002.02024.x
Subject(s) - nerve growth factor , neurotrophin , antibody , western blot , human skin , immunohistochemistry , endocrinology , medicine , basal (medicine) , chemistry , microbiology and biotechnology , pathology , biology , immunology , diabetes mellitus , biochemistry , receptor , genetics , gene
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 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 0.1–12.0, 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 NTR . The different molecular forms derived from prepro‐NGF are likely to be of importance in sensory mechanisms, and deserve further investigation.