Functional role of alpha7 nicotinic receptor in physiological control of cutaneous homeostasis.
Non-neuronal nicotinic acetylcholine receptors (nAChRs) are abundantly expressed in skin and their function remains to be elucidated. Herein, we report that cutaneous alpha7 nAChR plays a role in the physiological control of cutaneous homeostasis. We studied in vitro effects of functional inactivation of alpha7 receptor on the expression of apoptosis regulators in keratinocytes (KC) lacking alpha7 nAChR, and extracellular matrix regulators in the skin of alpha7 knockout (KO) mice. Elimination of the alpha7 component of nicotinergic signaling in KC decreased relative amounts of the pro-apoptotic Bad and Bax at both the mRNA and the protein levels, suggesting that alpha7 nAChR is coupled to stimulation of keratinocyte apoptosis. The skin of alpha7 KO mice featured decreased amounts of the extracellular matrix proteins collagen 1alpha1 and elastin as well as the metalloproteinase-1. Taken together, these results suggest an important role for alpha7 nAChR in mediating plethoric effects of non-neuronal acetylcholine on cutaneous homeostasis.
Arredondo
Juan
J
Department of Dermatology, University of California, Davis, 4860 Y Street, #3400, Sacramento, CA 95817, USA.
Nguyen
Vu Thuong
VT
Chernyavsky
Alexander I
AI
Bercovich
Dani
D
Orr-Urtreger
Avi
A
Vetter
Douglas E
DE
Grando
Sergei A
SA
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D012879:Skin Physiological Phenomena; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D003094:Collagen; D004549:Elastin; D020782:Matrix Metalloproteinases