title: The platelet-derived growth factor receptor/STAT3 signaling pathway regulates the phenotypic transition of corpus cavernosum smooth muscle in rats.
abstract: Erectile dysfunction (ED) is a common clinical disease that is difficult to treat. We previously found that hypoxia modulates the phenotype of primary corpus cavernosum smooth muscle cells (CCSMCs) in rats, but the underlying molecular mechanism is still unknown. Platelet-derived growth factor receptor (PDGFR)-related signaling pathways are correlated with cell phenotypic transition, but research has been focused more on vascular smooth muscle and tracheal smooth muscle and less on CCSMCs. Here, we investigated the role of PDGFR-related signaling pathways in penile CCSMCs, which were successfully isolated from rats and cultured in vitro. PDGF-BB at 5, 10, or 20 ng/ml altered CCSMC morphology from the original elongated, spindle shape to a broader shape and promoted the synthetic phenotype and expression of the related proteins vimentin and collagen-I, while inhibiting the contractile phenotype and expression of the related proteins smooth muscle (SM) α-actin (α-SMA) and desmin. Inhibition of PDGFR activity via siRNA or the PDGFR inhibitor crenolanib inhibited vimentin and collagen-I expression, increased α-SMA and desmin expression, and considerably inhibited serine-threonine protein kinase (AKT) and signal transducer and activator of transcription 3 (STAT3) phosphorylation. STAT3 knockdown promoted the contractile phenotype, inhibited vimentin and collagen-I expression, and increased α-SMA and desmin expression, whereas AKT knockdown did not affect phenotype-associated proteins. STAT3 overexpression in CCSMC cells weakened the suppressive effect of PDGFR inhibition on the morphology and phenotypic transformation induced by PDGF-BB. Through activation of the PDGFR/STAT3 signaling pathway, PDGF promoted the synthetic phenotype transition; thus, regulation of this pathway might contribute to ED therapy.
authors.affiliation: The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Yan
authors.affiliation: The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Huang
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Zhao
authors.affiliation: Andrology Laboratory on Integration of Chinese and Western Medicine, Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine, Hangzhou, China.|Central Laboratory, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Fu
authors.affiliation: The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Gao-Yue
authors.initials: GY
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
authors.affiliation: Department of Urology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.|Andrology Laboratory on Integration of Chinese and Western Medicine, Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine, Hangzhou, China.
authors.forename: Bo-Dong
authors.initials: BD
authors.lastname: Lv
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D015687:Cell Hypoxia; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007172:Erectile Dysfunction / Q000188:drug therapy; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010413:Penis / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014746:Vimentin / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D014746:Vimentin; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt