The Role of Wnt Pathways in Pulmonary Senescence: Regulation of PPARy

Although PPARy seems to play an important role in the differentiation and function of a great variety of pulmonary cell types, the question remains: why would PPARy level and activity alter with age? Pinpointing the initial molecular trigger is difficult but recent studies highlighted the imbalance in Wnt signalling as age progresses [94]. Importantly, the opposition between PPARy and the Wnt / p-catenin pathway has already been reported in several tissues by multiple research groups including ourselves [95]. It is conceivable that the pulmonary (epithelial) setting is similar in showing reciprocal changes of PPARy and Wnt expression or activity with age. Indeed, increased Wnt4 and Wnt5a secretion in the ageing lung has been observed and both Wnts were reported to down-regulate PPARy using a different mechanism [unpublished observations]. Reduction in PPARy also leads to a decreased number of the alveolar progenitor or ATII cells; which can explain age-associated reduction in regenerative capacity. As ATII cells are also the source of surfactants, reduction in SP-levels indicates weakened functionality of ATII-s that was documented in both ageing animals as well as in the primary human lung tissue [96].

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