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Despite the debilitating and lethal nature of pulmonary hypertension (PH) secondary to interstitial lung disease (group 3 PH),1 research into the treatment of this unique category of vasculopathy remains in a relatively nascent stage compared with that of pulmonary arterial hypertension (PAH, group 1). A clue to uncovering the underlying pathophysiology of this particular subtype of group 3 PH, however, may be found in overlapping interest in the DNA damage response (DDR) shared by both pulmonary fibrosis and PH researchers.2 Primarily a pathway dedicated to preventing DNA damage to cellular progeny, the DDR functions via a complex network of cell cycle checkpoint signalling and DNA repair mechanisms. In the context of malignancy, these non-redundant pathways can be exploited by dependent cancerous cells to thwart apoptosis, thus promoting survival and eventual metastasis.
Therapeutically, a key target of the DDR is the family of checkpoint kinases: CHK1 primarily affecting the prevention of DNA damage being replicated (resulting in G1/S-phase cell cycle arrest), and CHK2 mediating transmission to the next generation of cells (a G2/M-phase checkpoint).3 While there are examples of CHK regulation related to end-organ fibrosis, to date, there is a dearth of literature describing the role of CHK in lung fibrosis. …
Contributors AB wrote the manuscript; VdJP initiated, wrote and edited the manuscript.
Funding This work was supported by the National Institute of Health (NIH) R01 HL142776, R01 HL142887 (AB), R01 HL134776 and R01 HL139664 (VdJP.).
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.
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