DHH

Case study 1: Duojun Qiu, 2023

This study explored the effects and potential mechanism by which PBX/knotted 1 homeobox 1 (PKNOX1) may exacerbate stomach adenocarcinoma (STAD). In vitro, we measured cell viability, proliferation, migration, and invasion using cell counting kit-8, colony formation, wound healing, and cell migration assays, respectively. Real time qPCR and western blotting assessed the mRNA and protein levels of PKNOX1, Snail, vimentin, N-cadherin, E-cadherin, desert hedgehog (DHH), cyclin D2, glioma-associated oncogene homolog 1, and smoothened.

Downregulation of PKNOX1 inhibited STAD cell viability, proliferation, migration, invasion, and epithelial-mesenchymal transition. Upregulation of TEAD4 promoted colony formation and migration, while these effects were reversed by PKNOX1 depletion. Furthermore, PKNOX1 regulated the activation of the hedgehog signalling pathway at the gene level, as we identified PKNOX1 to be a putative transcription factor for DHH that promotes its expression.

Fig1. PKNOX1 regulates the Hh signalling pathway. DHH, CCND2, GLI1, and SMO protein levels as determined by western blot.

Fig2. Knockdown of PKNOX1 in STAD inhibits cells proliferation, migration, invasion, and EMT in a Hh signalling-dependent manner.

Case study 2: Pilar Chinchilla, 2010

The Hedgehog (Hh) pathway orchestrates developmental and homeostatic angiogenesis. the three Hh isoforms--Sonic Hedgehog (Shh), Indian Hedgehog (Ihh) and Desert Hedgehog (Dhh)--signal through patched-1 (ptCH1) and Smoothened (SMo), to activate the Gli transcription factors with a characteristic rank of potency (Shh >> Ihh > Dhh). To dissect the mechanisms through which Hh proteins promote angiogenesis, the researchers analyzed processes inherent to vessel formation in endothelial cells.

The results showed that none of the Hh ligands were able to induce Gli-target genes in human umbilical vein (HUVeC) or human cardiac microvascular endothelial cells (HMVeC). However, the three Hh proteins promote endothelial cell tubulogenesis in 3D cultures in a SMo- and Gi protein-dependent manner. Consistent with the required cytoskeletal re-arrangement for tubulogenesis, Shh, Ihh and Dhh all stimulated the small GTPase RhoA and the formation of actin stress fibers. In addition to regulating the actin cytoskeleton, the Hh ligands promoted survival through inhibition of the pro-apoptotic effect of PTCH1 in a SMO-independent manner.

Fig3. Tubulogenesis in Matrigel induced by Shh, Ihh and Dhh was quantified as number of tubes and number of nodes per field of n = 3 experiment

Fig4. Actin filaments were stained with phalloidin-rhodamin in serum-starved HUVeC cells (control) and cells stimulated with 1 μg/ml Shh, Ihh and Dhh for 15 min.

Fig1. Schematic representation of PKNOX1's putative role in STAD. (Duojun Qiu, 2023)

Fig2. Schematic models of the three alternative modes of HH processing, secretion and presentation. (Christopher A Pettigrew, 2014)

DHH involved in several pathways and played different roles in them. We selected most pathways DHH participated on our site, such as Hedgehog signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with DHH were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

DHH has several biochemical functions, for example, calcium ion binding, patched binding, peptidase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by DHH itself. We selected most functions DHH had, and list some proteins which have the same functions with DHH. You can find most of the proteins on our site.

DHH has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with DHH here. Most of them are supplied by our site. Hope this information will be useful for your research of DHH.