| A Rho-associated coiled-coil kinase (ROCK) is identified as a critical downstream effector of GTPase RhoA which
contains two isoforms, ROCK1 (also known as p160ROCK and ROKβ) and ROCK2 (also known as Rho-kinase and
ROKα), the gene of which is placed on chromosomes 18 (18q11.1) and 2 (2p24), respectively. ROCKs have a
principal function in the generation of actin-myosin contractility and regulation of actin cytoskeleton dynamics.
They represent a chief role in regulating various cellular functions, such as apoptosis, growth, migration, and
metabolism through modulation of cytoskeletal actin synthesis, and cellular contraction through phosphorylation of numerous downstream targets. Emerging evidence has indicated that ROCKs present a significant
function in cardiac physiology. Of note, dysregulation of ROCKs involves in several cardiac pathological processes like cardiac hypertrophy, cardiac fibrosis, systemic blood pressure disorder, and pulmonary hypertension.
Moreover, ROCKs, in addition to their role in regulating renal arteriolar contraction, glomerular blood flow, and
filtration, can also play a role in controlling podocytes, tubular cells, and mesangial cell structure and function.
Hyperactivity disorder and over-gene expression of Rho/ROCK have been indicated in different cancers.
Furthermore, it seems that increasing the expression of mRNA or ROCK protein has an undesirable effect on
patient survival and has a positive impact on the progression and worsening of disease prognosis. This review
focuses on the physiological and pathological functions of ROCKs with a particular view on its possible value of
ROCK inhibitors as a new therapy in cancers and non-cancer diseases. |