TY - JOUR
T1 - Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease
AU - Kashyap, Sonu
AU - Zeidler, Julianna D.
AU - Chini, Claudia C.S.
AU - Chini, Eduardo Nunes
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9
Y1 - 2020/9
N2 - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases implicated in the development of end stage renal disease (ESRD). Although FDA has recently approved a drug against ADPKD, there is still a great need for development of alternative management strategies for ADPKD. Understanding the different mechanisms that lead to cystogenesis and cyst expansion in ADPKD is imperative to develop new therapies against ADPKD. Recently, we demonstrated that caloric restriction can prevent the development of cystic disease in animal models of ADPKD and through these studies identified a new role for pregnancy associated plasma protein-A (PAPP-A), a component of the insulin-like growth factors (IGF) pathway, in the pathogenesis of this disease. The PAPP-A-IGF pathway plays an important role in regulation of cell growth, differentiation, and transformation and dysregulation of this pathway has been implicated in many diseases. Several indirect studies support the involvement of IGF-1 in the pathogenesis of ADPKD. However, it was only recently that we described a direct role for a component of this pathway in pathogenesis of ADPKD, opening a new avenue for the therapeutic approaches for this cystic disease. The present literature review will critically discuss the evidence that supports the role of components of IGF pathway in the pathogenesis of ADPKD and discuss the pharmacological implications of PAPP-A-IGF axis in this disease.
AB - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases implicated in the development of end stage renal disease (ESRD). Although FDA has recently approved a drug against ADPKD, there is still a great need for development of alternative management strategies for ADPKD. Understanding the different mechanisms that lead to cystogenesis and cyst expansion in ADPKD is imperative to develop new therapies against ADPKD. Recently, we demonstrated that caloric restriction can prevent the development of cystic disease in animal models of ADPKD and through these studies identified a new role for pregnancy associated plasma protein-A (PAPP-A), a component of the insulin-like growth factors (IGF) pathway, in the pathogenesis of this disease. The PAPP-A-IGF pathway plays an important role in regulation of cell growth, differentiation, and transformation and dysregulation of this pathway has been implicated in many diseases. Several indirect studies support the involvement of IGF-1 in the pathogenesis of ADPKD. However, it was only recently that we described a direct role for a component of this pathway in pathogenesis of ADPKD, opening a new avenue for the therapeutic approaches for this cystic disease. The present literature review will critically discuss the evidence that supports the role of components of IGF pathway in the pathogenesis of ADPKD and discuss the pharmacological implications of PAPP-A-IGF axis in this disease.
KW - Autosomal dominant polycystic kidney disease (ADPKD)
KW - Insulin growth factor binding protein (IGFBP)
KW - Insulin like growth factors (IGFs)
KW - Metalloproteases
KW - Pregnancy associated plasma protein-A (PAPP-A)
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U2 - 10.1016/j.cellsig.2020.109698
DO - 10.1016/j.cellsig.2020.109698
M3 - Review article
C2 - 32569826
AN - SCOPUS:85086925986
SN - 0898-6568
VL - 73
JO - Cellular Signalling
JF - Cellular Signalling
M1 - 109698
ER -