[HTML][HTML] Fibrosis: ultimate and proximate causes

VJ Thannickal, Y Zhou, A Gaggar… - The Journal of clinical …, 2014 - Am Soc Clin Investig
VJ Thannickal, Y Zhou, A Gaggar, SR Duncan
The Journal of clinical investigation, 2014Am Soc Clin Investig
Fibrotic disorders account for an increasing burden of disease-associated morbidity and
mortality worldwide. Although numerous risk factors have been recognized, the etiologies of
many of these clinical syndromes have not been identified, and they are often termed
idiopathic or cryptogenic. Here, we provide an evolutionary perspective on fibrosis aimed at
elucidating its etiopathogenesis. By asking the ultimate question of “why” this process
evolved in multicellular organisms, we hope to uncover proximate explanations for “how” it …
Fibrotic disorders account for an increasing burden of disease-associated morbidity and mortality worldwide. Although numerous risk factors have been recognized, the etiologies of many of these clinical syndromes have not been identified, and they are often termed idiopathic or cryptogenic. Here, we provide an evolutionary perspective on fibrosis aimed at elucidating its etiopathogenesis. By asking the ultimate question of “why” this process evolved in multicellular organisms, we hope to uncover proximate explanations for “how” it causes disease in humans. We posit that physiological fibrosis-like reactions evolved as an essential process in host defense against pathogens and in normal wound healing. Based on this premise, we reason that pathological fibrosis is related to one or more of the following: unidentified infectious or noninfectious antigens, autoimmunity, impaired regenerative responses, and the antagonistically pleiotropic action of genes involved in wound healing or development. The importance of genetic susceptibility, epigenetics, aging, and the modern-day environment are highlighted. Consideration of both ultimate and proximate causation goes beyond philosophical cogitations, as it will better inform pathobiological mechanisms of disease and aid in the prevention and treatment of fibrotic diseases.
The Journal of Clinical Investigation