Megakaryocyte/platelet-derived TGF-β1 inhibits megakaryopoiesis in bone marrow by regulating thrombopoietin production in liver.

ABSTRACT: Transforming growth factor β1 (TGF-β1) regulates a wide variety of events in adult bone marrow (BM), including quiescence of hematopoietic stem cells, via undefined mechanisms. Because megakaryocytes (MKs)/platelets are a rich source of TGF-β1, we assessed whether TGF-β1 might inhibit its own production by comparing mice with conditional inactivation of Tgfb1 in MKs (PF4Cre;Tgfb1flox/flox) and control mice. PF4Cre;Tgfb1flox/flox mice had ∼30% more MKs in BM and ∼15% more circulating platelets than control mice (P < .001). Thrombopoietin (TPO) levels in plasma and TPO expression in liver were approximately twofold higher in PF4Cre;Tgfb1flox/flox than in control mice (P < .01), whereas TPO expression in BM cells was similar between these mice. In BM cell culture, TPO treatment increased the

SUBMITTER: Gostynska S 

PROVIDER: S-EPMC9198906 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature