http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Novel mutations of CDKN1C in Japanese patients with Beckwith-Wiedemann syndrome
Hitomi Yatsuki,Ken Higashimoto,Kosuke Jozaki,Kayoko Koide,Junichiro Okada,Yoriko Watanabe,Nobuhiko Okamoto,Yoshinobu Tsuno,Yoko Yoshida,Kazutoshi Ueda,Kenji Shimizu,Hirofumi Ohashi,Tsunehiro Mukai,Hid 한국유전학회 2013 Genes & Genomics Vol.35 No.2
Beckwith-Wiedemann syndrome (BWS) is an imprinting-related human disease that is characterized by macrosomia, macroglossia, abdominal wall defects, and variable minor features. BWS is caused by several genetic/epigenetic alterations, such as loss of methylation at KvDMR1,gain of methylation at H19-DMR, paternal uniparental disomy of chromosome 11, CDKN1C mutations, and structural abnormalities of chromosome 11. CDKN1C is an imprinted gene with maternal preferential expression, encoding for a cyclin-dependent kinase (CDK) inhibitor. Mutations in CDKN1C are found in 40 % of familial BWS cases with dominant maternal transmission and in *5 % of sporadic cases. In this study, we searched for CDKN1C mutations in 37BWS cases that had no evidence for other alterations. We found five mutations—four novel and one known—from a total of six patients. Four were maternally inherited and one was a de novo mutation. Two frame-shift mutations and one nonsense mutation abolished the QT domain, containing a PCNA-binding domain and a nuclear localization signal. Two missense mutations occurred in the CDK inhibitory domain,diminishing its inhibitory function. The above-mentioned mutations were predicted by in silico analysis to lead to loss of function; therefore, we strongly suspect that such anomalies are causative in the etiology of BWS.
Chieko Taguchi,Fuyuki Sato,Chen Wang,Shigeru Nakamura,Kosuke Oikawa,Ujjal Kumar Bhawal,Hiroyuki Okada,Kazumune Arikawa 조선대학교 치의학연구원 2022 Oral Biology Research (Oral Biol Res) Vol.46 No.4
Aberrant wound closure occurs in a broad range of wounds and scars, and the altered regulation of transcription factors in wound areas can account for both of those conditions. This study aimed to explore the function of the transcription factor Smad3 in wound healing using a tongue wound model in Smad3 knockout (Smad3–/–) mice and with Smad3 small interfering RNA (siRNA) transfected human gingival fibroblasts (HGFs). Smad3 –/–mice were used to examine the extent of repair in tongue wounds. Cell migration was evaluated in HGFs using wound healing assays. The mRNA expression levels of Sox2, E-cadherin, fibronectin, and vimentin were examined in HGFs using reverse transcription-quantitative polymerase chain reaction. Histopathological analysis of wound closure in Smad3–/– mice showed rapid re-epithelialization and remodeling in tongue wound repair compared with Smad3+/+ mice. Increased numbers of neutrophils were identified in the wounds of Smad3 –/– mice. Sox2 and phospho-E-cadherin expression levels were increased in Smad3–/– mice. Smad3 knockdown by siRNA increased cell migration of HGFs. In addition, Sox2, E-cadherin, fibronectin, and vimentin mRNA levels were significantly increased in Smad3 siRNA-transfected HGFs compared with controls. Collectively, these findings demonstrate that a Smad3 deficiency can expedite wound healing and increase immune reactions and extracellular matrix formation after tongue injuries, boosting recovery through Sox2 and E-cadherin. Consequently, Smad3 inhibition would help stimulate tongue wound healing.