Hedgehog (Hh) signaling plays essential roles in animal development and tissue homeostasis, and its misregulation causes congenital diseases and cancers. Regulation of the ubiquitin/proteasome-mediated proteolysis of Ci/Gli transcription factors is central to Hh signaling, but whether deubiquitinase is involved in this process remains unknown. Here, we show that Hh stimulates the binding of a u...

Complex body plans require sophisticated cell–cell signaling pathways. How these pathways evolved is often not very well understood. Here, we argue that the Hedgehog (Hh) signaling pathway may have arisen from systems that were originally designed for the transport and homeostasis of certain bacterial sterol analogs—the hopanoids. We propose a possible scenario for the evolution of Hh signaling...

AIM The purpose of this project was to evaluate the influence of circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs) on blood platelet function in experimental hypertension associated with hypercholesterolemia. METHODS Golden Syrian hamsters were divided in six groups: (i) control, C; (ii) hypertensive-hypercholesterolemic, HH; (iii) 'prevention', HHin-EPCs, HH ...

Hedgehog (Hh) pathway inhibition in cancer has been evaluated in both the ligand-independent and ligand-dependent settings, where Hh signaling occurs either directly within the cancer cells or within the nonmalignant cells of the tumor microenvironment. Chondrosarcoma is a malignant tumor of cartilage in which there is ligand-dependent activation of Hh signaling. IPI-926 is a potent, orally del...

برای دستیابی به مزیت رقابتی در شرایط عدم‌­اطمینان که آن تغییر ضروری است، یکی از چالش‌های بزرگ سازمان‌ها کاهش ریسک طریق ایجاد زنجیره‌های تأمین تاب‌آور است. تاب‌آوری زنجیره ‌تأمین توانایی مقابله با اختلال اشاره دارد یک رویداد غیرقابل‌پیش‌بینی بوده و دارای منابع داخلی خارجی مختلفی ازجمله بلایای طبیعی ریسک‌های عملیاتی پژوهش حاضر شبیه‌سازی توسط نرم‌افزار ارنا زنجیره‌ سنگ ساختمانی «کارخانه سنگبری آسم...

Hedgehog (HH) signaling is essential for vertebrate and invertebrate embryogenesis. In Drosophila, feedback upregulation of the HH receptor Patched (PTC; PTCH in vertebrates), is required to restrict HH signaling during development. By contrast, PTCH1 upregulation is dispensable for early HH-dependent patterning in mice. Unique to vertebrates are two additional HH-binding antagonists that are i...

Hedgehog (HH) signaling has emerged as a critical pathway involved in the pathogenesis of a variety of tumors. As a result, HH antagonists are currently being evaluated as potential anticancer therapeutics. Conversely, activation of HH signaling in the adult heart may be beneficial, as HH agonists have been shown to increase coronary vessel density and improve coronary function after myocardial...

Hedgehog (Hh) signaling has been implicated in the development of osteoblasts and osteoclasts whose balanced activities are critical for proper bone formation. Since many mouse mutants in the Hh pathway are embryonic lethal, questions on the exact effects of Hh signaling on osteogenesis remain. Using zebrafish larvae mutant in Indian Hedgehog, patched1, patched2 and suppressor of fused (dre), w...

Hedgehog (Hh) moves from the producing cells to regulate the growth and development of distant cells in a variety of tissues. Here, we have investigated the mechanism of Hh release from the producing cells to form a morphogenetic gradient in the Drosophila wing imaginal disk epithelium. We describe that Hh reaches both apical and basolateral plasma membranes, but the apical Hh is subsequently i...