| First Author | Gostynska S | Year | 2022 |
| Journal | Blood Adv | Volume | 6 |
| Issue | 11 | Pages | 3321-3328 |
| PubMed ID | 35358295 | Mgi Jnum | J:326879 |
| Mgi Id | MGI:7315155 | Doi | 10.1182/bloodadvances.2021005977 |
| Citation | Gostynska S, et al. (2022) Megakaryocyte/platelet-derived TGF-beta1 inhibits megakaryopoiesis in bone marrow by regulating thrombopoietin production in liver. Blood Adv 6(11):3321-3328 |
| abstractText | Transforming growth factor beta1 (TGF-beta1) 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-beta1, we assessed whether TGF-beta1 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 approximately 30% more MKs in BM and approximately 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 number of MKs from wild-type mice by approximately threefold, which increased approximately twofold further in the presence of a TGF-beta1-neutralizing antibody and increased the number of MKs from PF4Cre;Tgfb1flox/flox mice approximately fourfold. Our data reveal a new role for TGF-beta1 produced by MKs/platelets in regulating its own production in BM via increased TPO production in the liver. Additional studies are required to determine the mechanism. |
