Dihydropyridine calcium channel blockers are frequently used in therapy of hypertension. Among many side effects, Dihydropyridine has been found associated with gingival overgrowth that usually occurs within one third of the patients. Nifedipine, the first generation of dihydropyridine, causes the gingival overgrowth through androgen receptor (AR)/collagen cascade in dihydropyridine induced gingival overgrowth (DIGO) patients. The rennin-angiotensin system is a hormone system that also regulates blood pressure and fluid balance. We propose that angiotensin II (Ang II) is an intermediate inducer to cause the gingival overgrowth in hypertension patients. The aim of this project is to verify the mechanism of Ang II regulates AR/collagen axis through angiotensin II type I receptor (AT1R) in DIGO. Our further study will evaluate the therapeutic efficiency of angiotensin-converting enzyme (ACE) inhibitor and AT1R antagonists for DIGO cell. There are four specific aims will be addressed here: Year 1: Aim 1: To clarify the mechanism of RAS on AR regulation in gingival fibroblast under the stimulation of IL-1β and/or nifedipine; Aim 2: To verify the inter-relationship of TGF-β1 and AR in RAS/AT1R/AR axis as DIGO cells are stimulated by IL-1β and/or nifedipine. Year 2: Aim 1: To further verify the RAS/AT1R/TGFβ1/AR/collagen axis in DIGO fibroblast; Aim 2: To characterize the mechanism that ACE inhibitors and AT1R antagonists inhibit collagen expression by decreasing RAS/AT1R/TGFβ1/AR activity. We expect ACE inhibitors and AT1R antagonists act as a potential therapeutic drug for the prevention and treatment of DIGO by suppressing AR activity, and subsequently reducing collagen over production. In the near future, the results of this study can imply that ACE inhibitors and AT1R antagonists are promising potential chemopreventive and chemotherapeutic agents for DIGO.
|Effective start/end date||8/1/17 → 7/31/18|
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