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Interplay between HTRA1 and classical signalling pathways in organogenesis and diseases.

Chio Oka1, Razwa Saleh2, Yasumasa Bessho3

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|May 9, 2022
PubMed
Summary

High temperature requirement factor A1 (HTRA1), a serine protease, regulates key cell processes and signaling pathways. Its dysregulation links to diseases, making HTRA1 a potential therapeutic target for conditions like cancer and AMD.

Keywords:
HTRA inhibitorsHTRA1NOTCHPreeclampsiaTGF-βWNT

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cell Biology

Background:

  • High temperature requirement factor A1 (HTRA1) is a crucial serine protease involved in fundamental biological processes.
  • HTRA1 regulates cell proliferation, migration, and fate, and manages protein aggregates via refolding, translocation, or degradation.
  • Mutations in HTRA1 are associated with numerous disorders, highlighting its significance in disease pathogenesis.

Purpose of the Study:

  • To review the role of HTRA1 in key signaling pathways, including transforming growth factor beta (TGF-β), Wingless/Integrated (WNT), and NOTCH.
  • To examine the involvement of HTRA1 in organogenesis and the pathogenesis of diseases such as preeclampsia, age-related macular degeneration (AMD), small vessel disease, and cancer.
  • To explore therapeutic strategies targeting HTRA1 for managing these disorders.

Main Methods:

  • Literature review of scientific articles focusing on HTRA1 function and its role in signaling pathways.
  • Analysis of HTRA1's involvement in cellular processes like proliferation, migration, and protein aggregate control.
  • Examination of disease associations and potential therapeutic targets related to HTRA1.

Main Results:

  • HTRA1 significantly modulates TGF-β, WNT, and NOTCH signaling pathways.
  • HTRA1's function is critical during organogenesis and implicated in the development of preeclampsia, AMD, small vessel disease, and cancer.
  • Dysregulation of HTRA1 contributes to various pathological conditions.

Conclusions:

  • HTRA1 is a key regulator of essential cellular functions and developmental processes.
  • The serine protease activity of HTRA1 is implicated in multiple human diseases.
  • Targeting HTRA1 presents a promising therapeutic avenue for a range of disorders.