The Effect Of MTMR14 On Asthma And Cardiac Hypertrophy

MTMR14 is a novel phosphoinositide phosphatase.Its most specific substrates are a series of phospholipids,not proteins,which is the most specific biological characteristics.MTMR14 is highly expressed in multiple tissues,such as skeletal muscle,testis,airway smooth muscle and heart.The deletion of MTMR14 caused a series of disease,such as centronuclear myopathy,skeletal muscle cell aging,atherosclerosis,muscle weakness and fatigue,etc.However,the role of MTMR14played in asthma and cardiac hypertrophy is unclear.MTMR14 wildtype（WT）and knockout（KO）mice were used as animal models.1.The effect of MTMR14 on asthma.Theovalbumin（OVA）-sensitized model of asthma caused airway inflammation and remodeling in mice.The Real-time PCR results showed that MTMR14 was down-regulated in airway smooth muscle（ASM）,bronchial smooth muscle（BSM）and lung of asthmatic mice.Consequentially,the expression of MTMR14 was assayed by immunohistochemical staining.The results showed that MTMR14 was down-regulated in trachea of OVA-sensitized mice.The techniques for[Ca²⁺]_i measurements in ASMCs using TILL imaging system.We found the deletion of MTMR14 led to[Ca²⁺]_i increased in ASMCs.In addition,patch-clamp results showed that the dysfunction of L-type calcium channels in ASMCs of MTMR14 KO mice.2.The effect of MTMR14 on cardiac hypertrophy.We isolated primary cells from heart of newborn mice successfully.Immunofluorescence experiments showed that the purity of primary myocardial cells is very high,nearly 100%.Real-time PCR results showed that ANP,BNP andβ-MHC was up-regulated after Ang II treatement.Next research demonstrated that MTMR14 is expressed in H9C2 cells.Ang II induced up-regulation of ANP,BNP andβ-MHC mRNA expression in H9C2 cells and enlargement of H9C2 cells surface area.The present study demonstrated that Ang II-induced H9C2 cells showed a significant increase in I_Ca,Lcurrent density.Taken together,the deletion of MTMR14 may lead to asthma.And I_Ca,La,L current density was significantly increased in AngII-induced H9C2 cells.