Role of parathyroid hormone-related protein in the regulation of stretch-induced renal vascular smooth muscle cell proliferation.
In vivo, vascular smooth muscle cells (VSMC) are continuously exposed to mechanical cyclic stretch as a result of the pulsatile blood flow from the cardiac contractile cycle. Stretch is altered in pathologic conditions and contributes to vascular remodeling by modulating VSMC proliferation and death. Parathyroid hormone-related protein (PTHrP) is a locally produced poly-protein that regulates cell growth. It was shown previously that PTHrP inhibits VSMC proliferation through the auto/paracrine pathway by interacting with its receptor, the PTH1R, but stimulates VSMC proliferation through the intracrine pathway by translocating into the nucleus. In the current study, VSMC that were isolated from both resistance and compliance vessels were used to study the role of PTHrP in VSMC proliferation under experimental stretch. It is shown that PTHrP gene expression is upregulated by stretch and that PTHrP opposes the inhibitory effect induced by stretch on VSMC proliferation through the intracrine pathway. In addition, it is demonstrated that PTHrP expression is controlled at the post-transcriptional level by stretch. Taken together, these results strongly suggest that PTHrP plays a critical role in the modulation of VSMC proliferation in response to stretch. Thus, in conditions in which stretch is increased, such as in hypertension or in restenosis after angioplasty, PTHrP may contribute to vessel hyperplasia.
Schordan
Eric
E
Pharmacologie et Physiologie Rénovasculaires (Equipe Mixte INSERM-ULP 0015), 11 rue Humann, Bâtiment 4, 1er étage, F67085 Strasbourg Cedex, France.
Welsch
Sandra
S
Rothhut
Sylvie
S
Lambert
Alain
A
Barthelmebs
Mariette
M
Helwig
Jean-Jacques
JJ
Massfelder
Thierry
T
D000818:Animals; D001011:Aorta / Q000166:cytology; D002455:Cell Division / Q000502:physiology; D015870:Gene Expression; D006977:Hypertension, Renal / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology*; D009924:Organ Culture Techniques; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000166:cytology; D013314:Stress, Mechanical
D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger