Thsd4, encoding ADAMTSL6 (a member of the ADAMTS/L superfamily), is a microfibril-associated protein that promotes fibrillin-1 matrix assembly [2]. It is involved in multiple biological processes and associated with several pathways. In the extracellular matrix (ECM) context, it contributes to maintaining ECM homeostasis, and is related to processes like epidermal-mesenchymal interactions, which are crucial for normal tissue development and function.

In aged hair follicles, Thsd4 is highly downregulated in the dermal papilla (DP) extracellular matrix. Thsd4 is specifically expressed at the interface between DP and hair matrix (HM). Mouse models have shown that it promotes hair growth by enhancing the interaction between dermal (DP) and epithelial cells (HM) through the SDC4-THSD4-CXCL1 signaling axis [1]. In the context of aortic diseases, Thsd4+/- mice show progressive dilation of the thoracic aorta. Histologic examination reveals typical medial degeneration and diffuse disruption of the extracellular matrix, highlighting its role in aortic physiology and the pathogenesis of thoracic aortic aneurysm [2].

In conclusion, Thsd4 is essential for promoting hair growth by facilitating epidermal-mesenchymal interactions during aging. In the context of aortic diseases, Thsd4 haploinsufficiency in mouse models reveals its importance in maintaining aortic integrity. These model-based studies of Thsd4 provide valuable insights into hair growth regulation and the pathogenesis of aortic diseases, potentially guiding the development of new therapies in these areas.