title: Expression Profiles of Neuropeptides, Neurotransmitters, and Their Receptors in Human Keratocytes In Vitro and In Situ.
abstract: Keratocytes, the quiescent cells of the corneal stroma, play a crucial role in corneal wound healing. Neuropeptides and neurotransmitters are usually associated with neuronal signaling, but have recently been shown to be produced also by non-neuronal cells and to be involved in many cellular processes. The aim of this study was to assess the endogenous intracellular and secreted levels of the neuropeptides substance P (SP) and neurokinin A (NKA), and of the neurotransmitters acetylcholine (ACh), catecholamines (adrenaline, noradrenaline and dopamine), and glutamate, as well as the expression profiles of their receptors, in human primary keratocytes in vitro and in keratocytes of human corneal tissue sections in situ. Cultured keratocytes expressed genes encoding for SP and NKA, and for catecholamine and glutamate synthesizing enzymes, as well as genes for neuropeptide, adrenergic and ACh (muscarinic) receptors. Keratocytes in culture produced SP, NKA, catecholamines, ACh, and glutamate, and expressed neurokinin-1 and -2 receptors (NK-1R and NK-2R), dopamine receptor D2, muscarinic ACh receptors, and NDMAR1 glutamate receptor. Human corneal sections expressed SP, NKA, NK-1R, NK-2R, receptor D2, choline acetyl transferase (ChAT), M3, M4 and M5 muscarinic ACh receptors, glutamate, and NMDAR1, but not catecholamine synthesizing enzyme or the α1 and β2 adrenoreceptors, nor M1 receptor. In addition, expression profiles assumed significant differences between keratocytes from the peripheral cornea as compared to those from the central cornea, as well as differences between keratocytes cultured under various serum concentrations. In conclusion, human keratocytes express an array of neuropeptides and neurotransmitters. The cells furthermore express receptors for neuropeptides/neurotransmitters, which suggests that they are susceptible to stimulation by these substances in the cornea, whether of neuronal or non-neuronal origin. As it has been shown that neuropeptides/neurotransmitters are involved in cell proliferation, migration, and angiogenesis, it is possible that they play a role in corneal wound healing.
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Marta
authors.initials: M
authors.lastname: Słoniecka
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Le Roux
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Boman
authors.affiliation: Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.
authors.forename: Berit
authors.initials: B
authors.lastname: Byström
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden; Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden; Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Danielson
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D065306:Corneal Injuries / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000096:biosynthesis*; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis*
chemical_list: D009479:Neuropeptides; D018377:Neurotransmitter Agents; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter