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CHK yourself, before you wreck yourself: targeting the DNA damage response in secondary pulmonary hypertension
  1. Andrew Bryant1,
  2. Vinicio de Jesus Perez2
  1. 1 Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
  2. 2 Medicine, Stanford University, Stanford, California, USA
  1. Correspondence to Dr Vinicio de Jesus Perez, Medicine, Stanford University, Stanford, California, USA; vdejesus{at}

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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. …

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  • 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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