Hepatocellular senescence induces multi-organ senescence and dysfunction via TGF
Research article published in Nature cell biology (2024)
Abstract
Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood. Here we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence using liver injury models and genetic models of hepatocyte-specific senescence. In patients with severe acute liver failure, we show that the extent of hepatocellular senescence predicts disease outcome, the need for liver transplantation and the occurrence of extrahepatic organ failure. We identify the TGFβ pathway as a critical mediator of systemic spread of senescence and demonstrate that TGFβ inhibition in vivo blocks senescence transmission to other organs, preventing liver senescence induced renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence, which, independent of ageing, contributes to multi-organ dysfunction.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Резюме
Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing.
Почему это важно для гирудотерапии
This study used liver injury models, genetic models of hepatocyte-specific senescence, and patient data from severe acute liver failure to demonstrate that hepatocellular senescence can spread systemically via TGFβ signaling, inducing senescence and dysfunction in extrahepatic organs such as the kidney. TGFβ inhibition in vivo blocked this inter-organ transmission and prevented renal dysfunction. The article has no direct connection to hirudotherapy or leech secretome research; no leeches or leech-derived molecules are mentioned. The TGFβ pathway is studied here in the context of senescence and multi-organ dysfunction, and the abstract provides no data linking it to any leech-related therapeutic application. Relevance to ASH's domain is absent based on the abstract alone.
Цитирование
Hepatocellular senescence induces multi-organ senescence and dysfunction via TGF
Kiourtis C et al. · Nature cell biology, 2024
Связанный клинический контекст
Узнайте, как это исследование связано с клинической практикой
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