PAPP-A2 nowy regulator procesu wzrastania

Abstract

Short stature is the main problem that paediatric endocrinologists have to grapple with. Endocrine disorders account for only 5% of patients with short stature, but this is still one of the most common causes of reports to the endocrine clinic and hospitalisation in the endocrine department. A properly functioning growth hormone/insulin-like growth factor 1 (GH/IGF1) axis is one of the most important factors in proper growth. A lot of genetic defects in this axis lead to syndromes marked by impaired growth, like Laron syndrome, mutations in the STAT5B, insulin-like growth factor 1 (IGF1), and insulin-like growth factor 1 receptor (IGF1R) and mutations in the acid labile subunit (ALS). Two proteases important for the proper functioning of the GH/IGF1 axis: pregnancy-associated plasma protein-A (PAPP-A) and pregnancy-associated plasma protein-A2 (PAPP-A2), have been described. The first description of the new syndrome of growth failure associated with mutation in the PAPP-A2 gene was given by Andrew Dauber et al. This review evaluates the current data concerning PAPP-A2 function, and particularly the effect of PAPP-A2 mutation on growth. (Endokrynol Pol 2017; 68 (6): 682-687)

Effects of GH/IGF on the Aging Mitochondria

“…Among the many actions of GH in liver, its major role is stimulating the transcription of the IGF-1 gene, the IGF-binding proteins (IGFBPs) [6], and the acid labile subunit (ALS) that carry IGF-1 in circulation [7]. Other members of this axis are the proteases that release the IGF-1 from its complex with IGFBPs, pregnancy-associated plasma protein A (PAPP-A), and the PAPP-A2 [8]. The somatotropic axis is tightly regulated under normal physiological conditions.…”

Hsa_circ_0015382 is involved in the pathogenesis of preeclampsia by mediating THBS2 expression

“…7,8 The pregnancy-associated plasma protein A2 (PAPPA2) is a pivotal mediator of cell growth. 9 Furthermore, PAPPA2 expression is increased in PE and could be involved in the invasion and migration of trophoblast. 10,11 A circRNA circ_0111277 formed by back-splicing of the PAPPA2 mRNA precursor has been revealed to reduce trophoblast invasion and migration by regulating the HTRA1/Notch-1 pathway.…”

“…Previous studies show that circRNAs could regulate trophoblast proliferation, epithelial‐mesenchymal transition (EMT), migration and invasion in PE 7,8 . The pregnancy‐associated plasma protein A2 (PAPPA2) is a pivotal mediator of cell growth 9 . Furthermore, PAPPA2 expression is increased in PE and could be involved in the invasion and migration of trophoblast 10,11 .…”

Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults

“…Pappa2 gene encoding PAPP-A2 is on chromosome 1q25.2, contains five exons, and is approximately 382.4 kb with a 4.4 kb transcript. Several lines of evidence suggest that PAPP-A2 is important for the growth and postnatal development in animals and humans [16]. Ablation of Pappa2 in mice resulted in the retardation of postnatal growth with normal size at birth [17].…”