Transglutaminase type 2 is involved in the hematopoietic stem cells homeostasis
| Autor: | C Agrati, Manuela D’Eletto, Gustavo P. Amarante-Mendes, Oleg N. Demidov, Mauro Piacentini, Nickolai A. Barlev, V Bordoni, Primavera Borelli, Serafina Oliverio, Jackeline Soares de Oliveira Beltran, Luca Occhigrossi, Federica Rossin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
autophagy RHOA Settore BIO/06 MAP Kinase Signaling System Cells Knockout Inbred C57BL Biochemistry 03 medical and health sciences Mice MEDULA ÓSSEA DE ANIMAL TG2 GTP-Binding Proteins medicine Animals Protein Glutamine gamma Glutamyltransferase 2 Progenitor cell Cells Cultured Mice Knockout 0303 health sciences Transglutaminases Cultured biology 030302 biochemistry & molecular biology Autophagy Hematopoietic stem cell Cell Differentiation General Medicine Hematopoietic Stem Cells Cell biology Hematopoiesis Mice Inbred C57BL Haematopoiesis medicine.anatomical_structure biology.protein Female Bone marrow Stem cell |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Type 2 transglutaminase (TG2) is a multifunctional protein involved in various biological processes playing a key regulatory role in cell homeostasis such as cell death and autophagy. New evidence is emerging that support an important role of autophagy in regulating normal hematopoiesis. Prompted by these findings, in this study we investigated in vivo involvement of TG2 in mouse hematopoiesis under normal or nutrient deprivation conditions. We found that the number and rate of differentiation of bone marrow hematopoietic stem cell was decreased in the TG2 knockout mice. We present evidence showing that these effects on hematopoietic system are very likely due to the TG2-dependent impairment of autophagy. In fact, stimulation of autophagy by starvation is able to rescue the block of the differentiation of stem cells progenitors in the TG2 KO mice. It was also shown that the RhoA/ERK½ pathway, known to be essential for regulation of the bone marrow progenitor cells homeostasis, was significantly impaired in the absence of TG2. Hence, this study expanded our knowledge about TG2 discovering a role of this enzyme in regulation of hematopoiesis. |
| Databáze: | OpenAIRE |
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