MDM4: A Novel Molecular Target for Treating Idiopathic Pulmonary Fibrosis Associated with Aging
DOI:
https://doi.org/10.61427/jcpr.v1.i2.2021.25Keywords:
Idiopathic Pulmonary Fibrosis, MDM4, MyofibroblastAbstract
Idiopathic pulmonary fibrosis (IPF) is the end stage of many diffuse parenchymal lung diseases typified by excessive matrix deposition leading to destruction of normal lung architecture and function of unknown etiology. Aging is considered as a strong risk factor and an independent prognostic factor for progression of IPF. However, the exact mechanisms that link the IPF with aging remained unknown, but a number of changes associated with aging revealed in IPF lungs. The p53 gene is a tumour suppressor gene that played a vital role in cancer and it is also known to have activity in fibrosis. MDM2 and MDM4 are the two major inhibitors of p53 .They only differ in their intrinsic E3-ligase activity and promote degradation of p53. MDM4 is a matrix stiffness -regulated negative regulator of p53 highly expressed in fibrotic lesions of IPF. Some of the invitro studies reported that MDM4-p53 pathway promoted lung fibrosis resolution in aged mice, this suggests that MDM4 can be better target against persistent lung fibrosis associated with aging. Also, better knowledge of the pathophysiological mechanisms linking aging to IPF may provide new therapeutic windows to treat this devastating disease.
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