PMID- 26673553
OWN - NLM
STAT- MEDLINE
DCOM- 20171013
LR  - 20181113
IS  - 1460-2202 (Electronic)
IS  - 0271-3683 (Print)
IS  - 0271-3683 (Linking)
VI  - 41
IP  - 8
DP  - 2016 Aug
TI  - Transforming Growth Factor Beta 1 Modulates the Functional Expression of the 
      Neurokinin-1 Receptor in Human Keratocytes.
PG  - 1035-1043
AB  - PURPOSE: Transforming growth factor beta 1 (TGF-beta1) is a cytokine involved in a 
      variety of processes, such as differentiation of fibroblasts into myofibroblasts. 
      TGF-beta1 has also been shown to delay the internalization of the neurokinin-1 
      receptor (NK-1 R) after its activation by its ligand, the neuropeptide substance 
      P (SP). NK-1 R comprises two naturally occurring variants, a full-length and a 
      truncated form, triggering different cellular responses. SP has been shown to 
      affect important events in the cornea - such as stimulating epithelial cell 
      proliferation - processes that are involved in corneal wound healing and thus in 
      maintaining the transparency of the corneal stroma. An impaired signaling through 
      NK-1 R could thus impact the visual quality. We hypothesize that TGF-beta1 modulates 
      the expression pattern of NK-1 R in human corneal stroma cells, keratocytes. The 
      purpose of this study was to test that hypothesis. METHODS: Cultures of primary 
      keratocytes were set up with cells derived from healthy human corneas, obtained 
      from donated transplantation graft leftovers, and characterized by 
      immunocytochemistry and Western blot. Immunocytochemistry for TGF-beta receptors and 
      NK-1 R was performed. Gene expression was assessed with real-time polymerase 
      chain reaction (qPCR). RESULTS: Expression of TGF-beta receptors was confirmed in 
      keratocytes in vitro. Treating the cells with TGF-beta1 significantly reduced the 
      gene expression of NK-1 R. Furthermore, immunocytochemistry for NK-1 R 
      demonstrated that it is specifically the expression of the full-length isotype of 
      the receptor that is reduced after treatment with TGF-beta1, which was also 
      confirmed with qPCR using a specific probe for the full-length receptor. 
      CONCLUSIONS: TGF-beta1 down-regulates the gene expression of the full-length variant 
      of NK-1 R in human keratocytes, which might impact its signaling pathway and thus 
      explain the known delay in internalization after activation by SP seen with 
      TGF-beta1 treatment.
FAU - Roux, Sandrine Le
AU  - Roux SL
AD  - a Department of Integrative Medical Biology , Umea University , Umea , Sweden.
FAU - Borbely, Gabor
AU  - Borbely G
AD  - a Department of Integrative Medical Biology , Umea University , Umea , Sweden.
FAU - Sloniecka, Marta
AU  - Sloniecka M
AD  - a Department of Integrative Medical Biology , Umea University , Umea , Sweden.
AD  - b Department of Clinical Sciences, Ophthalmology , Umea University , Umea , 
      Sweden.
FAU - Backman, Ludvig J
AU  - Backman LJ
AD  - a Department of Integrative Medical Biology , Umea University , Umea , Sweden.
FAU - Danielson, Patrik
AU  - Danielson P
AD  - a Department of Integrative Medical Biology , Umea University , Umea , Sweden.
AD  - b Department of Clinical Sciences, Ophthalmology , Umea University , Umea , 
      Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151216
PL  - England
TA  - Curr Eye Res
JT  - Current eye research
JID - 8104312
RN  - 0 (Receptors, Neurokinin-1)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Blotting, Western
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Corneal Keratocytes/cytology/*metabolism
MH  - Female
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - RNA/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Neurokinin-1/biosynthesis/*genetics
MH  - Signal Transduction
MH  - Transforming Growth Factor beta1/biosynthesis/*genetics
PMC - PMC4989870
OTO - NOTNLM
OT  - Cornea
OT  - cytokines
OT  - neuropeptides
OT  - stroma
OT  - substance P
EDAT- 2015/12/18 06:00
MHDA- 2017/10/14 06:00
PMCR- 2016/08/18
CRDT- 2015/12/18 06:00
PHST- 2015/12/18 06:00 [pubmed]
PHST- 2017/10/14 06:00 [medline]
PHST- 2015/12/18 06:00 [entrez]
PHST- 2016/08/18 00:00 [pmc-release]
AID - 1088954 [pii]
AID - 10.3109/02713683.2015.1088954 [doi]
PST - ppublish
SO  - Curr Eye Res. 2016 Aug;41(8):1035-1043. doi: 10.3109/02713683.2015.1088954. Epub 
      2015 Dec 16.