Here we show that Pin1, a peptidyl-prolyl cis/trans isomerase which catalyzes the isomerization of phosphorylated Ser/Thr-Pro, is a regulatory molecule of thrombopoiesis. We found that mice lacking the Pin1 gene (Pin1 mice) formed more megakaryocytes (MKs) than wild type mice (WT mice), and that the proplatelet formation of MKs was poorer in Pin1 mice than WT mice. Treatment of Meg-01 cells, a megakaryoblastic floating cell line, with shRNA against Pin1 suppressed the proplatelet formation. Expression of tau, a microtubule associated protein was induced in MKs during proplatelet formation. Pin1 bound tau and promoted microtubule polymerization. Our results show that Pin1 serves as a positive regulatory molecule of proplatelet formation of MKs by enhancing the function of phosphorylated tau.
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http://dx.doi.org/10.1016/j.bbrc.2017.09.115 | DOI Listing |
Blood Adv
January 2025
The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cytoskeletal remodeling and mitochondrial bioenergetics play important roles in thrombocytopoiesis and platelet function. Recently, α-actinin-1 mutations have been reported in patients with congenital macrothrombocytopenia. However, the role and underlying mechanism of α-actinin-1 in thrombocytopoiesis and platelet function remain elusive.
View Article and Find Full Text PDFThromb Haemost
December 2024
Division of Hematology, Faculty of Medicine, Excellence Center in Translational Hematology, Chulalongkorn University, Bangkok, Thailand.
Background: Megakaryocytes (MK) from Bernard-Soulier syndrome (BSS) induced pluripotent stem cells (iPSCs) yielded reduced numbers but increased sizes of platelets. The molecular mechanisms remain unclear. This study aims to determine roles of signaling molecules involved in this process.
View Article and Find Full Text PDFStem Cell Res Ther
November 2024
Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, the Second Affiliation Hospital, School of Medicine, South China University of Technology, No.1 Panfu Road, Guangzhou, 510180, People's Republic of China.
Br J Pharmacol
February 2025
The SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Background And Purpose: The CAPEOX (combination of oxaliplatin and capecitabine) chemotherapy protocol is widely used for colorectal cancer treatment, but it can lead to chemotherapy-induced adverse effects (CRAEs).
Experimental Approach: To uncover the mechanisms and potential biomarkers for CRAE susceptibility, we performed whole-genome sequencing on normal colorectal tissue (CRT) before adjuvant chemotherapy. This is followed by in vivo and in vitro verifications for selected gene and CRAE pair.
Biochem Med (Zagreb)
October 2024
Institute of General Medicine, Samara State Medical University of the Ministry of Health of the Russian Federation, Samara, Russia.
Structural and functional alterations in platelets are an actual problem that requires more attention. The treatment of these illnesses proves challenging, inefficient and heavily relies on platelet donations. A difficult task confronting science is producing platelets , which calls for meticulous examination of factors affecting platelet generation.
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