BACKGROUND: Administration of topical rapamycin (RPM) suppresses the regeneration and revascularization of photocoagulated blood vessels induced by pulsed dye laser (PDL). OBJECTIVE: To systematically elucidate the molecular pathophysiology of the inhibition of PDL-induced angiogenesis by topical RPM in a rodent model. METHODS: The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of ribosomal protein S6 kinase (P70S6K) in rodent skin were examined with or without topical RPM administration post-PDL exposure. RESULTS: The PDL-induced systematic increases in transcriptional levels of angiogenic genes showed a peak expression at days 3-7 post-PDL in rodent skin. Topical application of 1% RPM significantly and systematically suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes during the first five days post-PDL. The phosphorylation levels of P70S6K increased after PDL exposure but those increases were suppressed by the topical RPM. After topical application, RPM penetrated to an approximate depth of 768.4 μm into rodent skin. CONCLUSION: Topical application of 1% RPM can significantly and systematically suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in a rodent model.
BACKGROUND: Administration of topical rapamycin (RPM) suppresses the regeneration and revascularization of photocoagulated blood vessels induced by pulsed dye laser (PDL). OBJECTIVE: To systematically elucidate the molecular pathophysiology of the inhibition of PDL-induced angiogenesis by topical RPM in a rodent model. METHODS: The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of ribosomal protein S6 kinase (P70S6K) in rodent skin were examined with or without topical RPM administration post-PDL exposure. RESULTS: The PDL-induced systematic increases in transcriptional levels of angiogenic genes showed a peak expression at days 3-7 post-PDL in rodent skin. Topical application of 1% RPM significantly and systematically suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes during the first five days post-PDL. The phosphorylation levels of P70S6K increased after PDL exposure but those increases were suppressed by the topical RPM. After topical application, RPM penetrated to an approximate depth of 768.4 μm into rodent skin. CONCLUSION: Topical application of 1% RPM can significantly and systematically suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in a rodent model.
Authors: Rong Yin; Shawn J Rice; Jinwei Wang; Lin Gao; Joseph Tsai; Radean T Anvari; Fang Zhou; Xin Liu; Gang Wang; Yuxin Tang; Martin C Mihm; Chandra P Belani; Dong-Bao Chen; J Stuart Nelson; Wenbin Tan Journal: Histol Histopathol Date: 2018-10-10 Impact factor: 2.303
Authors: W Tan; J Wang; F Zhou; L Gao; R Yin; H Liu; A Sukanthanag; G Wang; M C Mihm; D-B Chen; J S Nelson Journal: Br J Dermatol Date: 2017-11-16 Impact factor: 11.113
Authors: Rong Yin; Lin Gao; Wenbin Tan; Wei Guo; Tao Zhao; Jhon Stuart Nelson; Gang Wang Journal: Am J Dermatopathol Date: 2017-10 Impact factor: 1.533
Authors: M Ingmar van Raath; Jojanneke E van Amesfoort; Martin Hermann; Yasin Ince; Maurice J Zwart; Agustina V Echague; Yan Chen; Baoyue Ding; Xuan Huang; Gert Storm; Michal Heger Journal: J Clin Transl Res Date: 2019-05-01