POSTN Enhances the Proliferation of Goat Skin Fibroblasts Through the TGFβ Pathway Activation

ABSTRACT Skin exhibits regional structural and functional heterogeneity, but the underlying molecular mechanisms remain poorly understood. Here, we investigated the role of periostin (POSTN), an extracellular matrix (ECM)‐associated protein, in skin regionalization and fibroblast function in goats. Histological analysis revealed significant site‐specific differences in skin thickness, with the forehead showing the greatest dermal and epidermal thickness, coinciding with elevated POSTN protein expression. In cultured fibroblasts, POSTN knockdown impaired cell proliferation, migration, and ECM production, accompanied by downregulation of proliferation markers ( CCND1 , PCNA , and Ki67 ) and ECM genes ( COL1A1 and COL1A2 ). RNA‐seq analysis revealed that POSTN deficiency altered transcriptional profiles, notably suppressing genes related to the ECM and TGFβ signaling pathways. Activation of the TGFβ pathway via trimethylamine N‐oxide (TMAO) enhanced fibroblast proliferation and ECM gene expression, and partially rescued the defects induced by POSTN knockdown. These findings identify POSTN as a key regulator of fibroblast activity and regional skin specialization, likely acting through modulation of ECM composition and TGFβ signaling, offering novel insights into dermal homeostasis and skin heterogeneity.