From cooperation to collapse: systemic failure in liver disease through a sociological lens

The liver operates as a highly coordinated microsystem, where various liver cell types engage in dynamic interactions to maintain homeostasis. This intercellular cooperation resembles sociological models of sustainable cooperation, encompassing mechanisms such as resource sharing, communication netw...

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Bibliographic Details
Main Authors: Junyu Wang, Jingting Lei, Martin C. Harmsen, Han Moshage
Format: Article
Language:English
Published: Open Exploration Publishing Inc. 2025-07-01
Series:Exploration of Digestive Diseases
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Online Access:https://www.explorationpub.com/uploads/Article/A100580/100580.pdf
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Summary:The liver operates as a highly coordinated microsystem, where various liver cell types engage in dynamic interactions to maintain homeostasis. This intercellular cooperation resembles sociological models of sustainable cooperation, encompassing mechanisms such as resource sharing, communication networks, and conflict resolution. However, both in biology and sociology, cooperation can break down due to external pressures and self-serving behaviors. In metabolic dysfunction-associated steatotic liver disease (MASLD), chronic metabolic stress disrupts this equilibrium, leading to endothelial dysfunction, immune overactivation, and fibrosis—akin to sociological models of systemic collapse. A common model in sociology, Hardin’s Tragedy of the Commons, describes how individuals overexploit shared resources when acting in self-interest, ultimately leading to resource depletion. Similarly, under metabolic stress, hepatic cells prioritize short-term survival by increasing lipid storage, inflammatory signaling, and extracellular matrix (ECM) production. This self-serving response, much like free-riding in societal systems, exacerbates dysfunction, reinforcing a cycle of fibrosis and organ failure. Moreover, the failure in MASLD extends beyond the liver itself. The liver’s cooperative role is integral to its participation in inter-organ axes, including those with the cardiovascular, gut, brain, and kidney systems. While the analogy has limitations—cells do not possess intent as humans do—the fundamental principle of cooperation breakdown leading to systemic instability holds across disciplines. An interdisciplinary approach integrating biological and sociological insights offers novel perspectives for therapeutic innovation. Sociological frameworks provide concepts such as incentive structures and collective action, which can be applied to cellular behavior. By restoring cooperative cellular networks, therapies like extracellular vesicle (EV) treatment, ECM remodeling, and receptor (ant)agonists mimic interventions in social systems that rebuild trust and sustainability. This review explores how biological and sociological models of cooperation breakdown align and how regenerative medicine can leverage these insights to develop strategies that restore cellular equilibrium and halt disease progression.
ISSN:2833-6321