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2014 ; 124
(11
): 4673-7
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Fibrosis: ultimate and proximate causes
#MMPMID25365073
Thannickal VJ
; Zhou Y
; Gaggar A
; Duncan SR
J Clin Invest
2014[Nov]; 124
(11
): 4673-7
PMID25365073
show ga
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.
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